SeromYx

Biointron & Kactus Lunch & Learn: Antibody Series III

Mon, 04 May 2026 13:10:24 GMT

Type: Lunch & Learn

Date: May 8th, 2026 @ 11:30am

Location: Boston, MA

Biointron & Kactus Lunch & Learn: Antibody Series III

Join us at Biointron & Kactus 2026 Lunch & Learn : Antibody Series III - Precision Antibody Engineering! Explore the world of antibody technologies!

Explore expert perspectives, engage in dynamic discussions on cutting-edge innovations, and network with peers from across the industry. This session provides a collaborative space to share knowledge, uncover trends, and tackle the challenges driving the future of the field.

Our guest speakers will talk about:

Comprehensive Fc-Effector Function Profiling of Approved Anti-CD20 mAbs and Anti-HER2 ADCs
Critical Decisions for the Design of Cell-Based NAB Assays

Space is limited - reserve your spot today!

Can't make it in person? Watch a live Zoom recording here: https://us06web.zoom.us/meeting/register/dplEqcRfSoGL-JA-t-tUPg

PEGS Boston

Tue, 21 Apr 2026 16:29:26 GMT

Type: Conference

Dates: May 11th-15th, 2026

Location: Boston, MA

PEGS Boston 2026

The PEGS Boston Summit is where the future of biologics takes shape. For over 20 years, PEGS has been the go-to event for protein and antibody engineering, drug development, immunotherapy, radiotherapy, and AI/ML-driven biologics research. New in 2026: a dedicated focus on peptides, spotlighting their therapeutic power, design innovations, and expanding role in drug discovery.

With 350+ presentations, breakout sessions, and interactive training seminars, PEGS delivers the insights and connections you need to stay ahead. The exhibit hall buzzes with top technology and service providers, giving you a front-row seat to the tools transforming the industry.

Presentation

Title: Optimizing Therapeutic Antibodies by Balancing the Safety and Efficacy of Their Fc-Mediated Effector Functions

Date: May 14th, 2026 at 3:40pm

Speaker: Amanda Gross, PhD., Associate Director, Immunology

Antibodies represent a rapidly expanding class of biotherapeutics, where Fc-mediated effector functions strongly influence clinical efficacy and safety. By restricting themselves to classical assays (ADCC, ADCP, CDC), current pipelines under-evaluate Fc functions elicited by other immune effectors like dendritic cells, macrophages, and granulocytes. Comprehensive Fc function profiling of established and novel antibody formats enables data-driven lead selection, optimization, and identification of clinical correlates, ultimately increasing clinical confidence.

Glycan pairing in therapeutic IgG orchestrates Fcγ receptor engagement and ADCC: an integrated structure-function approach for thorough evaluation of Fc N-glycans as critical quality attributes

Tue, 21 Apr 2026 16:23:38 GMT

The Fc Review:

Are we oversimplifying Fc glycosylation?

A recent study in mAbs explores how glycan pairing within IgG antibodies shapes Fcγ receptor engagement and ADCC, highlighting an often-overlooked layer of Fc biology.

Background:

Fc glycosylation is a well-known modulator of antibody function, influencing Fcγ receptor binding and downstream effector activity. However, each IgG contains two Fc glycans, one on each heavy chain, that can pair symmetrically or asymmetrically.

Most analytical approaches report glycan composition as an average, without capturing how these glycans are distributed across individual molecules.

This study asks a key question. Does glycan pairing itself influence Fc function?

The study highlights:

Fc glycan pairing, not just overall composition, influences Fcγ receptor binding across multiple receptors and allotypes
A single afucosylated glycan was sufficient to drive enhanced FcγRIIIa binding and ADCC, with limited additional benefit from full afucosylation
Galactosylation and high-mannose structures showed receptor- and context-dependent effects on Fc engagement
Functional outcomes cannot be fully inferred from bulk glycan profiles, as different pairing configurations can produce distinct biological behavior

Figure 1. Schematic illustration of the stepwise generation of asymmetrically glycosylated rituximab variants.

Implications for antibody development:

For antibody developers, these findings highlight an important consideration. Fc-mediated function is shaped not only by which glycans are present, but how they are arranged within each molecule.

Relying on averaged glycan measurements may overlook meaningful differences in Fc receptor engagement and effector function.

Our perspective:

This work reinforces a broader theme in antibody engineering. Fc biology is driven by combinations of structural features that work together to shape function.

Even well-characterized modifications such as afucosylation can have nuanced effects depending on how they are incorporated. Evaluating these features in isolation or as averaged properties may miss important aspects of antibody behavior.

Comprehensive Fc profiling helps capture these interactions and provides a clearer view of how design and production choices translate into functional immune responses.

References:

Meudt, M., Baumeister, J., Russell, A. C., Dzielak, L., Hansen, G., Mizaikoff, B., … Higel, F. (2026). Glycan pairing in therapeutic IgG orchestrates Fcγ receptor engagement and ADCC: an integrated structure-function approach for thorough evaluation of Fc N-glycans as critical quality attributes. mAbs , 18(1). https://doi.org/10.1080/19420862.2026.2652642

World Vaccine Congress US 2026

Mon, 06 Apr 2026 18:01:32 GMT

Moving Beyond Binding: Why Antibody Function Matters for Vaccine Efficacy

At World Vaccine Congress US, Ashley Brate, PhD (Associate Director, Immunology at SeromYx Systems), presented how shifting beyond traditional antibody measurements can provide a more complete understanding of vaccine-induced immunity.

While antibody binding and neutralization titers are widely used to assess vaccine responses, they do not fully capture protection. The presentation highlighted that individuals with similar antibody levels can experience very different outcomes , underscoring that the functional quality of the immune response is a key driver of efficacy.

Central to this is the role of Fc-mediated effector functions, which enable antibodies to engage immune cells and trigger mechanisms such as phagocytosis, cytotoxicity, and complement activation. These functions are highly diverse and involve multiple immune cell types, yet they are often under-characterized in vaccine development despite their importance in both efficacy and safety.

The session also emphasized that neutralization alone does not fully explain protection , particularly in early immune responses or against emerging variants. In some cases, protection is observed before neutralizing antibodies are detectable, pointing to additional immune mechanisms at play.

Overall, the presentation reinforced a key takeaway: antibodies must do more than bind, they must function. Incorporating comprehensive, antigen-specific functional profiling approaches, such as Systems Serology , is essential for identifying correlates of protection and advancing next-generation vaccine design.

NextGen Biomed Workshop 2026

Tue, 31 Mar 2026 12:57:10 GMT

Summary:

This workshop explores the sophisticated interplay between antibody engineering, receptor clustering, and Fc-mediated effector functions. As the industry moves beyond simple monoclonal antibodies, understanding how to control secondary interactions, whether through bispecific architectures or programmable synthetic motifs, is critical for enhancing tumor selectivity and de-risking clinical development.

Moderator:

Andrew Buchanan, PhD.

Session 1: Targeting Death Receptor 5 with Mono- and Bispecific Antibodies: Fc Receptor–Dependent Effects on Tumor and Normal Cells.

Speaker: Victor Goldmacher, Ph.D.

Activation of death receptor 5 (DR5) requires receptor clustering, which monospecific anti-DR5 IgG antibodies achieve only through secondary crosslinking mediated by FcγRIIB, a receptor expressed on B cells and other immune cells. This FcγRIIB dependence can produce apparent anti-tumor activity in xenograft models that may not translate clinically and may also raise concerns about off-tumor toxicity due to DR5 clustering on normal tissues. We developed IMV-M, a MUC16×DR5 bispecific apoptosis trigger that clusters DR5 directly on tumor cells through MUC16 binding, eliminating the need for FcγRIIB-mediated crosslinking. IMV-M demonstrated strong, MUC16-selective anti-tumor activity in vitro and in vivo without FcγRIIB interaction and showed no toxicity in a pilot non-human primate study. We will present our data and discuss the role of FcγRIIB-dependent crosslinking in the activity and interpretation of DR5-targeting antibodies and suggest a strategy to avoid this dependency; implications for FcγRIIB interactions of ADCs will also be discussed.

Session 2: Deep Fc Profiling of HER2-Targeting Antibodies: Derisking Linker Strategies for Synthetic Motif Conjugates and Uncovering Mechanistic Insights for Approved ADCs

Speaker: Shashi Jatiani, Ph.D.

The development of universal CAR-T systems relies on the precise orchestration of conjugated monoclonal antibodies acting as programmable adapters where the interplay between the synthetic motif and the engineered Fc region is critical for therapeutic control. This session explores the choice synthetic motif conjugation strategy to ensure the antibody acts as a precise bridge without triggering unintended biological interference, specifically focusing on decoupling endogenous immune activation from CAR-T engagement. By tuning Fc-effector function, detrimental immune triggers can be reduced or silenced to prevent CART cell fratricide and CRS, ensuring the primary therapeutic action remains driven by the CAR-T cells while still leveraging beneficial Fc-mediated efficacy. Complementing this, the session presents a separate set of data involving the deep Fc-effector profiling of approved HER2-targeting antibodies. This comprehensive comparative analysis of trastuzumab-based ADCs reveals how different linker-payload combinations influence FcγR and C1q binding dynamics, providing a high-resolution map of how established ADC architectures impact innate immune-modulating potential and safety de-risking.

*The recording will be available soon. Please register your interest here to receive it once it’s released.

Impacts of Antibody Structure and Mixtures on Receptor Signaling for Antibody-Dependent Cellular Cytotoxicity

Tue, 10 Mar 2026 17:27:25 GMT

The Fc Review:

How do antibody structure and binding dynamics shape ADCC signaling?

A recent study in The AAPS Journal explores how multiple antibody design features, including Fab affinity, hinge flexibility, Fc engagement, and antigen density, influence antibody-dependent cellular cytotoxicity (ADCC) signaling.

Background:

ADCC is a key mechanism of action for many therapeutic antibodies, yet the strength of this response depends on more than Fcγ receptor binding alone. Productive immune activation requires antibodies to bridge target cells and effector cells within the immune synapse, forming receptor crosslinks that trigger downstream signaling.

Using a combination of computational modeling and experimental data, this study examines how structural properties of antibodies influence these crosslinking events and ultimately shape ADCC signaling outcomes.

The study highlights:

ADCC signaling is influenced by multiple antibody properties, including Fab affinity, hinge flexibility, Fc receptor engagement, and antigen expression levels.
Antibody structure affects how efficiently Fc receptors and target antigens are crosslinked within the immune synapse.
In some cases, moderate Fab affinity supported stronger signaling by favoring productive crosslinking configurations.
Antibody valency and hinge flexibility also influenced signaling outcomes by altering the geometry of immune synapse interactions.

Fig. 1. Proposed kinetic model and antibody variants. A The kinetic model of IgG antibody interactions with an effector cell and an antigen expressing cancer cell. Reversible binding rates determine the interchange between the different states. The states include unbound antibody (Ab), antibody monovalently bound to antigen (M), antibody bivalently bound to two antigens (D), antibody with only the Fc domain bound to the Fc receptor (R), antibody crosslinking one antigen and Fc receptor (B), and a trivalently bound antibody with all three domains bound (T). The two Fab arms of the antibody bind to antigens with on- and off-rates (kon,Ag and koff,Ag). The Fc region engages Fc receptors with corresponding on- and off-rates (kon,Fc and koff,Fc). The antigen-bound antibody can interact with an additional receptor with a fitted effective binding rate (kon,M,Fc and kon,D,Fc). Upon cross-linking of the antibody between the effector cell and cancer cell (states B and T), effector cells are activated for immune induction, which is captured with Michaelis–Menten kinetics by C for the maximum response and Km for cross-linked receptors at half maximum signal. B The varied antibody parameters experimentally tested and modeled in this work include antibody isotype, Fab affinity, Fc affinity, hinge flexibility, and valency (single Fab arm). Figure was created in BioRender.

Implications for antibody development:

For developers designing antibodies with Fc-mediated mechanisms of action, these findings highlight the importance of considering how structural and binding parameters work together to drive effector cell activation.

ADCC potency is not governed by a single variable. Instead, it emerges from the combined effects of antibody affinity, geometry, receptor engagement, and antigen context.

Our perspective:

This study reinforces a key theme in antibody engineering: Fc-mediated function is highly context dependent. Small changes in affinity, hinge architecture, or receptor engagement can reshape how antibodies form immune synapses and activate effector pathways.

Comprehensive Fc profiling helps reveal these effects early, allowing teams to understand how design decisions translate into functional immune responses.

References:

Guan J, Wang T, Tessier PM, Thurber GM. Impacts of Antibody Structure and Mixtures on Receptor Signaling for Antibody-Dependent Cellular Cytotoxicity. The AAPS Journal. 2025;28:39.

Cross-species cellular mapping and humanization of Fcγ receptors to advance antibody modeling

Thu, 12 Feb 2026 14:15:13 GMT

The Fc Review:

How well do our preclinical models capture human Fc biology?

A new Science Immunology study takes a deep look at Fcγ receptor and FcRn expression across humans, non-human primates, and mice, highlighting how species-specific differences shape Fc-mediated immune function.

Background:

Fc-dependent activity is influenced not only by antibody design, but also by where and how Fcγ receptors are expressed across immune cell types and tissues. While animal models remain central to #antibody development, differences in Fcγ receptor biology across species can complicate interpretation of Fc-driven mechanisms.

The study highlights:

Species-specific differences in Fcγ receptor expression patterns across immune cell subsets and tissues.
Context-dependent regulation of Fcγ receptors by inflammatory cues, with expression shifting across cell types and environments.
These differences influence how Fc-mediated functions are engaged and interpreted across experimental systems.
Cross-species variation in FcγR and FcRn biology helps explain why Fc-dependent effects observed preclinically may not always translate cleanly to human settings.

Fig. 1. Fcγ receptors across species, their genomic mapping, and the characterization of a mouse model with humanized Fcγ receptors. The genomic organization of the Fc receptor locus in human, cynomolgus macaque (M. fascicularis), and mouse is shown according to the UCSC Genome Browser. Similar colors indicate genes that were predicted to be orthologs, and arrows indicate the orientation of the genes. Heat-shock proteins in the Fc receptor locus are not shown. In this resource, we mapped receptors at the protein and transcriptomic level and summarized the influence of cytokines and TFs on their expression. To bridge differences between species, we generated and characterized a mouse model carrying the major IgG-binding receptors.

Implications for antibody development:

For programs where Fc activity is central to mechanism of action, or intentionally minimized, this work reinforces the importance of understanding how Fc biology differs across species. Interpreting Fc-driven efficacy or safety signals requires careful consideration of receptor expression, cellular context, and experimental system.

Our perspective:

As Fc engineering strategies become more deliberate, evaluating Fc behavior in systems that reflect human immune biology becomes increasingly important. Broad functional assessment across relevant Fc pathways can help ensure that design decisions translate as intended as antibodies move toward the clinic.

References:

Lambrecht BN et al. Cross-species mapping of Fcγ receptor and FcRn expression reveals translational differences in antibody effector biology. Science Immunology , 2026.

Fc engineering by monoclonal mammalian cell display for improved affinity and selectivity towards FcγRs

Wed, 21 Jan 2026 15:13:43 GMT

The Fc Review:

How are antibody developers actually using Fc engineering today?

A recent analysis of the IMGT/mAb-DB database takes a systematic look at engineered Fc variants across therapeutic antibodies and fusion proteins, offering a real-world snapshot of how Fc design choices are being deployed in the clinic.

Background:

Fc engineering is often discussed in terms of individual mutations or isolated use cases. But at an industry level, it’s less clear how frequently Fc variants are used, which functions are prioritized, and whether antibodies rely on single or multiple Fc modifications. By mining curated entries in IMGT/mAb-DB, this study steps back to examine Fc engineering trends across approved and clinical-stage molecules.

The review highlights:

Fc engineering is widespread across therapeutic antibodies and fusion proteins cataloged in IMGT/mAb-DB
Effector silencing strategies are commonly employed, particularly in programs prioritizing safety and controlled immune engagement
Many molecules incorporate multiple Fc variants, rather than a single engineered change
Fc modifications are used across a range of mechanisms and formats, underscoring Fc’s role as an intentional design lever

Figure 2. Fc engineering by monoclonal mammalian cell display. (A) Schematic of the process. Fc library plasmids carrying error-prone mutagenesis at the hinge-CH2 region were introduced to RMCE ready CHO cells via aRMCE [34]. Transfected cells were incubated with Fcγ R bound beads for MACS to isolate IgG displaying cells. Post-MACS cells were screened by two rounds of FACS for the higher

affinity towards Fcγ RIIIa-F176, Fcγ RIIa, and Fcγ RIIb, respectively. (B) Ratiometric flow cytometry analysis of Fc WT and known variants with antigen EGFR-TNFα, individual Fcγ R-biotin, and SA-APC. (C) Ratiometric flow cytometry analysis of library cells during the screening procedures.

Implications for antibody development:

These data suggest that Fc engineering is no longer an exception, but a norm. As antibody programs increasingly rely on combinations of Fc mutations to tune activity, safety, and/or exposure, understanding how those changes behave together within a single Fc domain becomes critical. Developing Fc mutations in isolation and later combining them assumes additive behavior, an assumption that may not always hold and can lead to unexpected functional outcomes.

Even single, well-established Fc modifications can have effects beyond what they were introduced to achieve, highlighting the importance of evaluating Fc changes more broadly.

Our perspective:

As Fc design becomes more complex and purposeful, developers may benefit from evaluating engineered antibodies across broader functional contexts. Profiling Fc behavior across multiple receptors and immune pathways can help clarify how combined Fc variants translate into real biological outcomes, particularly early in development when design decisions are still flexible.

References:

Giudicelli V. et al. Identification of engineered IMGT Fc variants in IMGT/mAb-DB, a database of therapeutic antibodies and fusion proteins. mAbs, 2025. https://doi.org/xxxxx

Antibody Engineering & Therapeutics US 2025

Tue, 23 Dec 2025 17:40:15 GMT

Background:

Each antibody format introduces unique structural and functional variables that can significantly alter Fc effector activity. Assessing therapeutic antibodies on SeromYx’s high-throughput, GCLP-accredited Fc effector function platform enables empirical and format-agnostic profiling of developmental candidates. Our platform has helped uncover critical, early insights into the therapeutic activity and safety of diverse antibody formats, guiding development with data-driven decisions.

Generative design of antibody Fc-variants with synthetic and programmable functional profiles

Thu, 04 Dec 2025 15:01:17 GMT

The Fc Review:

Continuing our series taking a closer look at recent Fc-focused papers, what they found, and why it matters for antibody discovery and development.

Can we program the Fc region?

A recent bioRxiv preprint explores this question at scale, using millions of Fc variants to train machine learning models that predict functional outcomes across FcγR interactions.

Background:

Through engagement with Fc-receptors, the antibody Fc domain can direct a broad range of immune activities, including phagocytosis, cytokine release, antigen presentation, and immune cell polarization – each of which could be precisely tuned to combat disease. Fc engineering has traditionally focused on modifying one property at a time (E.g., ADCC, ADCP, or half-life). This work instead treats the Fc region as a functional design space and explores how sequence variations across the Fc domain can be linked to real immune engagement.

Fig. 1 | Development and characterization of an aglycosylated antibody Fc surface display system. a, Schematic of the antibody Fc yeast surface display approach. Image created with BioRender.com. b, Flow cytometry analysis of Fc-receptor binding in the yeast display system for wild-type human IgG1 Fc. X-axis: FLAG surface expression. Y-axis: Fc-receptor binding. Fc-receptors were used at a concentration of 50μg/mL. FcRn staining was performed at pH6. c, IgG1, aglycosylated Fc-variant 299A-IYG, and Fc null variant STR were stained across a titration series of each Fc-receptor. X-axis: Fc-receptor concentration. Y-axis: Fc-receptor binding (geometric mean fluorescence intensity) normalized to FLAG surface expression. Data were fitted using a sigmoidal (4-parameter logistic) curve. d, Radar plot showing the area under the binding curves from the Fc-receptor titration in panel c for IgG1, 299A-IYG, and STR.

The authors highlight:

Large-scale Fc variant screening enables learning sequence–function rules across multiple FcγRs
Deep-learning models trained on these data can predict receptor binding profiles based on Fc sequence
The study expands functional exploration of Fc sequence space beyond what has previously been examined
Multi-receptor binding patterns suggest that engineered Fc domains may need to be evaluated across multiple pathways, rather than relying on a single functional readout

Implications:

This work highlights a shift in how Fc engineering might evolve: instead of tweaking a known function, engineering may increasingly explore new functional profiles like tailored effector engagement, selective silencing, tissue targeting, or tunable immune activation. For developers advancing antibodies with Fc-dependent MOAs (or those designing Fc-silenced formats) this raises an important question:

How do we evaluate Fc behavior when relevant biology spans multiple immune pathways?

Our perspective:

As Fc formats evolve, the industry may move toward profiling Fc variants across broader biological contexts, including FcγR interactions, complement activity, and primary human immune cell engagement. That functional resolution could help guide engineering choices earlier, especially when Fc is central to MOA or purposefully silenced.

Human IgG Fc-engineering for enhanced plasma half-life, mucosal distribution and killing of cancer cells and bacteria

Thu, 20 Nov 2025 14:24:37 GMT

The Fc Review:

One Fc variant, three advantages?

A Nature Communications study demonstrates how a single Fc-engineered IgG achieved improved half-life, mucosal distribution, and enhanced immune-mediated killing, across both cancer and bacterial models.

Background:

Fc engineering is often discussed through a single lens, half-life extension, effector boosting, or silencing. This paper explores a broader question: can an Fc variant containing three point mutations deliver multiple functional gains across different biological systems?

The review highlights:

A modified Fc variant (Q311R/M428E/N434W) improved biodistribution in mucosal tissues.
Enhanced killing via complement and immune effector mechanisms was observed, even at low antigen levels.
Results were consistent across pathogen and oncology models, suggesting broad applicability of Fc design.

Implications:

Fc engineering can do more than optimize one pathway. Profiling engineered antibodies across multiple contexts may reveal capabilities not visible in single-endpoint assays.

Our perspective:

Understanding how Fc variants behave across different effector pathways is key to unlocking their full potential. Multiplexed profiling in human-relevant systems offers a way to uncover these effects early and guide design choices with confidence.

Want to catch up on previous entries in The Fc Review?

Access them here

SITC Poster 2025

Tue, 11 Nov 2025 13:35:26 GMT

Background:

Monoclonal antibodies (mAbs), bispecific antibodies (BsAbs) and antibody drug conjugates (ADCs) are key players in cancer immunotherapy. Beyond antigen targeting, their Fc regions mediate pivotal effector functions that significantly impact clinical efficacy and safety. Most developmental pipelines assess NK cell mediated antibody dependent cellular cytotoxicity (ADCC), monocyte mediated antibody dependent cellular phagocytosis (ADCP), and complement dependent cytotoxicity (CDC) but do not consider the Fc functions mediated by other immune effectors such as macrophages, neutrophils, basophils, eosinophils, and dendritic cells. A comprehensive understanding of Fc functions elicited by therapeutic antibodies can enable data-driven lead selection and optimization to increase confidence while progressing to the clinic.

Objective:

To establish a robust and systematic assessment strategy for Fc effector functions of therapeutic antibodies in oncology, and to demonstrate how this profiling enhances mechanistic insights, candidate design, and derisks clinical safety.

Methods:

Assay Platform: Combination of high throughput biophysical Fc receptor (FcR) binding assays and healthy human primary immune cell Fc functional assays to identify and quantify Fc effector functions including ADCC, ADCP, CDC, ADNP, ADEP, ADBP and ADDCP.
Fc Engineering Analysis: Integration of glycoengineering and Fc modification workflows to modulate effector profiles, with functional readouts driving lead selection.
Case Studies: Correlation of biophysical and cellular Fc function, discovery of novel Fc functions for approved mAbs, assessment of Fc-enhanced mAbs for function correlated with in vivo efficacy, mechanism of action (MoA) of therapeutic IgE, and confirmation of Fc silencing, via comprehensive assessment of immunological outcomes.

Results:

Biophysical C1q binding patterns showed strong correlations with complement deposition and complement activation leading to CDC.
Comprehensive profiling uncovered novel Fc functions of approved mAbs providing mechanistic insights into efficacy and safety.
Engineered Fc enhanced antibodies drove superior macrophage phagocytosis and NK cell activation, translating to improved tumor control in murine models.
Collaborative identification of the multi-cellular MoA for a first-in-class IgE clinical candidate.
Fc silencing preserved antigen binding while reducing off target cytotoxicity, minimizing cytokine release, and activation of inflammatory primary human immune cells.

Conclusion:

In oncology antibody development, balancing immune activation and safety is crucial. It is recommended to assess Fc effector function early in the process. The SeromYx platform, which includes biophysical and functional cell-based assays, offers key insights to guide Fc engineering, validate MoA, and support data-driven design by integrating the roles of both the Fab and Fc domains.

Authors:

Shashi Jatiani, PhD.

Design and engineering of bispecific antibodies: insights and practical considerations

Tue, 28 Oct 2025 15:02:55 GMT

The Fc Review:

How does Fc engineering shape bispecific antibody function?

A Frontiers in Bioengineering and Biotechnology review explores how the Fc region can be tuned to control effector function, half-life, and safety, key levers in the design of next-generation bispecific antibodies ( bsAbs ).

Background:

Bispecific antibodies bring new therapeutic possibilities by engaging multiple targets at once. But this complexity also brings new challenges, from unwanted immune activation to altered pharmacokinetics . The Fc region plays a central role here, acting as both a stabilizing scaffold and a regulator of immune effector engagement

The review highlights:

Fc engineering and glycoengineering can enhance or silence functions like ADCC and ADCP .
FcRn affinity tuning improves antibody half-life and tissue distribution.
Tailoring Fc interactions enables bispecifics with new modes of action, including targeted agonism and dual checkpoint blockade.

Implications:

Thoughtful Fc design is essential for achieving the right balance between potency, pharmacokinetics, and safety in bispecific development.

Our perspective:

This work underscores how small Fc changes can have big impacts on antibody function and therapeutic performance. At SeromYx, our platform is built to capture those effects, using primary-cell assays and multiplexed Fc profiling to reveal how engineered antibodies actually engage human effector pathways. For teams advancing bispecifics, that means earlier insight into how design choices translate to real biological outcomes.

Festival of Biologics 2025

Thu, 23 Oct 2025 14:23:22 GMT

Summary:

The arena of therapeutic antibodies is led by monoclonal antibodies (mAbs), bispecifics (BsAbs) and antibody drug conjugates (ADCs) with more complex Fc-containing formats currently gaining clinical traction. Antigen targeting remains the focus of candidate selection, however, Fc-mediated functions of antibodies significantly impact clinical efficacy and safety. Most developmental pipelines only assess Fc functions mediated by a narrow set of effectors, namely, NK cells (ADCC), monocytes (ADCP), and complement (CDC), but do not consider other immune effectors such as macrophages, neutrophils, basophils, eosinophils, dendritic cells, and platelets. A comprehensive assessment of Fc mediated functions can enable data-driven lead selection and optimization to advance the most promising candidates into the clinic with confidence.

Authors:

Shashi Jatiani, PhD.

An Fc-Engineered Glycomodified Antibody Supports Proinflammatory Activation of Immune Effector Cells and Restricts Progression of Breast Cancer

Thu, 23 Oct 2025 14:07:46 GMT

Abstract:

Fc engineering to enhance antibody effector functions harbors the potential to improve therapeutic effects. Understanding FcγR expression and distribution in the tumor microenvironment prior to and following treatment may help guide immune-engaging antibody design and patient stratification. In this study, we investigated FcR-expressing immune effector cells in HER2 ⁺ and triple-negative breast cancers (TNBC), including neoadjuvant chemotherapy–resistant disease. FcγRIIIa expression, FcγRIIIa ⁺ NK cells, and classically activated (M1-like) macrophages correlated with improved anti-HER2 antibody efficacy. FcγRIIIa protein and FcγRIIIa ⁺ NK cells and macrophages were present in primary TNBC and retained in treatment-resistant tumors.

FcγRIIIa was spatially associated with folate receptor alpha–positive (FRα+) tumor areas at baseline and in residual tumors following neoadjuvant chemotherapy. Wild-type and Fc-engineered antibodies recognizing two breast cancer–associated antigens, HER2 and the emerging TNBC target FRα, were designed and generated to have increased FcγRIIIa-expressing effector cell engagement. The combination of glycoengineering, including fucose removal from the N-linked Fc glycan, and Fc point mutations greatly increased antibody affinity for and retention on FcγRIIIa. The Fc-engineered antibodies enhanced immune effector activity against HER2+ breast cancer and TNBC, altering proinflammatory cytokine production by NK cells and tumor-conditioned macrophages and skewing macrophages toward proinflammatory states. Furthermore, the Fc-engineered antibodies restricted orthotopic HER2+ and FRα+ breast cancer xenograft growth at doses suboptimal for equivalent wild-type antibodies and recruited FcγRIIIa-expressing cells into tumors. Antibody design through combined glycoengineering and Fc point mutations to enhance FcγRIIIa engagement of tumor-infiltrating effector cells may be a promising strategy for developing therapies for patients with aggressive and treatment-resistant breast cancers.

Significance:

Assessment of Fc receptors and immune cells in breast cancer enables development of tailored engineering strategies for tumor-targeting monoclonal antibodies with enhanced immune-stimulating and anticancer attributes by combining glycoengineering and Fc mutations.

Authors:

Chenoweth, A. M., et al. (2025). An Fc-engineered glycomodified antibody supports proinflammatory activation of immune effector cells and restricts progression of breast cancer. Cancer Research.

Journal:

Cancer Research

New antibody restricts the growth of aggressive and treatment-resistant breast cancers

Thu, 23 Oct 2025 13:48:23 GMT

New antibody restricts the growth of aggressive and treatment-resistant breast cancers

A new potential antibody therapy strategy which restricts the growth of treatment-resistant breast cancers has been developed by scientists.

The King’s College London discovery, published today, could provide new treatment options for some of the most aggressive forms of breast cancer. This may be particularly important for patients whose cancers no longer respond to existing therapies, as well as those with triple-negative breast cancer – a subtype which lacks the receptors which are common drug targets, where treatment choices remain very limited.

The team designed an antibody that not only attacks the tumour cells directly, but also harnesses the body’s own immune defences. The first of its kind ‘triple-engineered antibody’, latches onto cancer cells on one end and draws in immune cells on the other.

While researchers have been modifying antibodies to boost their ability to activate immune cells, highly effective ones to be used for the treatment of breast cancer are still needed. The Breast Cancer Now Research Unit at King’s College London has been at forefront of this research for more than a decade. The group focuses on studying the patient’s immune system with a view of designing and testing innovative antibodies able to activate the patient’s immune response.

In their latest study, laboratory experiments and animal models revealed the modified antibody bound immune cells more strongly compared to current treatments. This activated the immune cells already present in the tumour to attack it, limiting the growth of tumours in triple-negative and treatment-resistant breast cancers.

The researchers also found that the modified antibody activated immune cells circulating in the bloodstream, which could boost the body’s overall ability to detect and fight cancer.

First author Dr Alicia Chenoweth, from the Faculty of Life Sciences & Medicine at King’s College London, said: “By making a few key changes in the structure of the antibody, we found that it could activate the immune system much more powerfully than an unmodified antibody currently used in breast cancer treatment.

“Many of the immune cells in breast tumours are in a ‘suppressed’ state, difficult to activate with unmodified antibodies. We found our triple-engineered antibodies were not only able to activate these immune cells to kill the cancer cells, but shifted these immune cells to a more ‘activated’ state overall.”

Lead author Professor Sophia Karagiannis, expert in Translational Cancer Immunology and Immunotherapy at King’s College London, who led this study said: “By examining key immune cell receptors in breast tumours, including those tumours resistant to chemotherapy and immunotherapy, we have designed our antibody to make them interact better and harness the immune system in a way that has never been done or tested in cancer before.

“If it proves successful, it could stimulate the immune system directly and address the significant unmet need we see in treatment resistant cancers including triple-negative breast cancer.”

Triple-negative breast cancer accounts for around 15 per cent of all breast cancers . It is a subtype that lacks receptors for the hormones oestrogen and progesterone and the HER2 protein, which are often treatment targets in other subtypes of breast cancer. As it lacks these targets, standard hormone therapies and drugs that target HER2 are ineffective, leaving patients with fewer treatment options and a higher risk of recurrence.

HER2-positive cancers are often treated with drugs, which improve outcomes for many patients, but the development of resistance remains a clinical challenge.

Dr Simon Vincent, chief scientific officer at Breast Cancer Now, said: “This promising, early-stage research offers hope for more and better treatments for over 8,000 women who are diagnosed with triple negative breast cancer each year in the UK.

“We know how urgently these women need new treatment options, as this form of the disease can be more challenging to treat, may be more likely to return or spread in the first few years following treatment, and it affects younger women and black women more than other groups. By funding research like this, we’re driving progress towards ensuring everyone with breast cancer lives and lives well.”

The team is now working towards developing immune-active antibodies so that one day these can be tested in patients in clinical trials. Further laboratory work is underway to optimise the therapy, including extending how long the antibody lasts in the body and ensuring it can activate a broader range of immune cell types.

The research not only highlights the potential of this therapy for breast cancer patients but could be used in other cancers. One of the antibody targets is also present in ovarian and endometrial cancers, so the approach might have clinical potential for these diseases too.

The study was published in Cancer Research , a journal of the American Association for Cancer Research

Notes to Editors

Funding:

Asda Tickled Pink fully funds Breast Cancer Now’s research unit at King’s College London, contributing over £1 million annually to advance knowledge of triple negative breast cancer - one of the hardest types to treat.

Industrial Partners:

SeromYx Systems, Inc., 299 Washington St, Ste D, Woburn, MA 01801 USA
Ludger, Ltd., Culham Campus, Abingdon, Oxfordshire OX14 3EB, United Kingdom;

Access to the full publication

World Vaccine Congress 2025

Tue, 21 Oct 2025 11:37:56 GMT

Summary:

Traditional vaccine evaluation often relies on binding or neutralization titers, yet these measures fail to capture the full spectrum of antibody functions that drive protection. SeromYx’s systems serology platform delivers the most comprehensive view of Fc-mediated effector functions, enabling developers to uncover correlates of protection, optimize lead selection, and de-risk clinical development.

Drawing on case studies from malaria, COVID-19, and more, this talk will highlight how functional antibody profiling reveals protective signatures overlooked by standard assays, and how these insights are reshaping next-generation vaccine and immunotherapeutic design. Attendees will gain a practical understanding of why going beyond binding is essential for tackling complex pathogens and advancing more effective, durable interventions.

Authors:

Ashley Brate, PhD.

Safety and immunogenicity of UB-612 heterologous booster in adults primed with mRNA, adenovirus, or inactivated COVID-19 vaccines: a randomized, active-controlled, Phase 3 trial

Mon, 15 Sep 2025 18:08:20 GMT

Background

Authorized COVID-19 vaccines require boosters for continued protection; however, the lack of crossplatform compatible boosters creates practical challenges to keeping populations protected.

Methods

This Phase 3, multicenter, international, randomized, active-controlled trial compared UB-612 as a thirddose heterologous booster to BNT162b2, ChAdOx1-S, or BBIBP-CorV homologous boosters in healthy subjects aged

≥16 years. Participants were randomly assigned 1:1 to receive a single intramuscular injection of UB-612 or an active comparator matching the primary dose, and were stratified for age, sex, N-protein seropositivity, and time since the last dose of their primary series COVID-19 vaccination. The primary objective was to show noninferiority of neutralizing antibody geometric mean titer (GMT) against live SARS-CoV-2 Wuhan strain after boosting with UB-612 or each of the licensed platform vaccines. Secondary and exploratory objectives covered short and long-term antibody responses. The safety analysis addressed subject and investigator reported adverse events. The study was registered on ClinicalTrials.gov, NCT05293665, and completed on September 12, 2023.

Findings

Between March 22 and September 9, 2022, 469 subjects received UB-612 as a heterologous booster, and 467 received BNT162b2 (n = 204), ChAdOx1-S (n = 95), or BBIBP-CorV (n = 168) as homologous boosters. Over 90% of all subjects were positive for N-protein antibody at baseline. When compared to the respective homologous booster response, UB-612 stimulated Wuhan and Omicron BA.5 neutralizing antibody responses that were non-inferior, thus meeting all primary and secondary immunogenicity endpoints of the study. Importantly, UB-612demonstrated superiority in neutralizing antibody GMT and seroresponse rates compared to ChAdOx1-S and BBIBP-CorV. UB-612 was also effective in stimulating neutralizing antibodies against a more recent Omicron XBB1.5 strain. Long-term immunity analysis through 6- and 12-month follow-ups favored UB-612 over ChAdOx1-S and BBIBP-CorV and supported comparable immunity to BNT162b2. All vaccines were well tolerated and had similar safety profiles.

Interpretation

In a pivotal Phase 3 study, UB-612 demonstrated the potential for broad use as a cross-platform heterologous booster, restoring protective immunity in adults previously vaccinated with mRNA, adenovirus vectored, or inactivated virus-based COVID-19 vaccines.

Funding

The study was co-funded by the Coalition for Epidemic Preparedness Innovations (CEPI) and Vaxxinity.

Authors:

Rumyantsev, A., et al. (2025). Safety and immunogenicity of UB-612 heterologous booster: A pivotal Phase 3 study. eClinicalMedicine, The Lancet.

Journal:

The Lancet

Impact of antibody Fc engineering on translational pharmacology, and safety: insights from industry case studies

Tue, 09 Sep 2025 14:57:36 GMT

The Fc Review:

Continuing our series taking a closer look at recent Fc-focused papers, what they found, and why it matters for antibody discovery and development.

How does Fc engineering shape the translation of antibodies from preclinical models to the clinic?

A new industry-wide review with 15 case studies examines the impact of Fc modifications on pharmacology and safety, and the challenges of predicting human outcomes from nonclinical studies.

Background:

Fc regions do not only extend half-life, they drive functions like ADCC , ADCP, CDC, and immune modulation. Engineering the Fc can enhance, silence, or redirect these activities. But the same changes that deliver potency can also introduce risk, especially when preclinical models do not fully mirror human Fc receptor biology.

The review highlights:

Species differences in FcγR and FcRn expression complicate translation from rodent and NHP models to humans.
Afucosylation and amino acid substitutions can strongly boost effector functions but may also uncover safety liabilities.
Fc silencing and half-life extension strategies require careful assessment to avoid unintended biology.
Case studies underscore the need for multi-pronged evaluation that combines specialized in vitro human primary-cell assays, transgenic models, and orthogonal biophysical methods such as SPR.

Implications:

The paper makes clear that Fc engineering is powerful, but its impact is context dependent. Translating nonclinical data requires assays that capture human biology and anticipate both efficacy and safety outcomes.

Our perspective:

Fc engineering can deliver meaningful gains, but each modification can ripple across multiple pathways from effector function to safety. That is why broad profiling across FcγR interactions, complement pathways, and primary-cell functions is essential. Evaluating engineered antibodies in a wide panel of human-relevant functional and biophysical assays, which form the core of SeromYx' assay portfolio, provides the clearest view of both intended effects and unanticipated trade offs.

SeromYx Systems Announces Strategic Collaboration with University of Pittsburgh to Advance CAR-T Therapy for Solid Tumors

Wed, 03 Sep 2025 14:41:40 GMT

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Fc gamma receptor polymorphisms in antibody therapy: implications for bioassay development to enhance product quality

Wed, 13 Aug 2025 14:42:22 GMT

The Fc Review:

Kicking off a new series where we take a closer look at recent Fc-focused papers. What they found, and why it matters for antibody discovery and development.

How much does FcγR genetic variation influence an antibody’s function?

A recent FDA review examines the often-overlooked role of Fcγ receptor (FcγR) polymorphisms in shaping therapeutic antibody activity, and the implications for the assays used to measure it.

Background:

FcγRs are the “effector arm” connection between antibodies and immune cells, driving processes like ADCC and ADCP. Genetic variation in these receptors can alter binding strength, modulate effector function, and impact clinical outcomes. Understanding this interplay is important for therapeutic design, potency assessment, and patient response prediction.

The review highlights:

Certain FcγR allotypes (e.g., FcγRIIIa-158V/F) can meaningfully shift clinical efficacy and should be considered early in development.
Primary-cell data provides context for how antibodies interact with real human immune systems, essential for understanding clinical potential.
Early incorporation of physiologically relevant systems enables detection of functional distinctions that may be missed in oversimplified models.
Orthogonal approaches like SPR/BLI provide valuable binding context to complement cell-based readouts.

Implications:

The paper underscores the need to balance biological relevance with assay consistency, and to consider receptor diversity early in the development pipeline.

Our perspective:

Evaluating antibodies in systems that reflect human immune responses from the start can reveal functional differences that might otherwise go unnoticed.

Fc-mediated Function Summit 2025

Thu, 07 Aug 2025 12:18:46 GMT

Summary:

The Fc domain plays a critical role in modulating the efficacy, safety, and pharmacology of antibody-based therapeutics and vaccines. Yet, most development pipelines assess only a narrow subset of Fc-mediated effector functions, risking missed opportunities and avoidable liabilities. In this presentation, Dr. Shashi Jatiani highlights how SeromYx’s high-throughput, physiologically relevant Fc profiling platform enables comprehensive evaluation of antibody function early in development.

Featuring case studies across mAbs, Fc-engineered variants - including clinical-stage and marketed antibodies, and other formats, the talk illustrates how expanded Fc profiling can inform lead selection, support mechanism-of-action studies, and derisk engineering strategies with clinical relevance.

Key Highlights:

Comprehensive Fc Profiling Enables Functional Characterization Beyond ADCC/ADCP: Expanded assessment of effector functions such as ADNP, ADEP, and complement activation uncovers mechanistic insights missed by conventional approaches.

Fc Engineering and Conjugation Strategies Require Functional Validation: Case studies demonstrate how antigen-specific FcγR binding and functional assays reveal unintended impacts of Fc silencing, half-life extension, and CAR-T conjugation methods.

Fab-Fc Interplay Influences Functional Potency: Data from large antibody libraries show that Fc function varies substantially across mAbs with identical Fc domains, emphasizing the need to assess effector activity alongside Fab affinity in lead optimization.

Summary:

As nearly all therapeutic antibodies move into the clinic with functional Fc domains, and over 45% of them Fc-engineered, developers can no longer afford to overlook the complexity and clinical impact of Fc-mediated effector functions.

This comprehensive workshop from NextGen Biomed 2025, led by Dr. Silvia Crescioli, Dr. Shashi Jatiani, and Dr. Ian Wilkinson ( GammaProteins ), walks through the nuanced interplay between Fab and Fc regions, the unpredictable consequences of Fc engineering, and why early, broad functional screening is critical for therapeutic success.

Highlights include:

Why silencing Fc function isn’t always truly silent
How tripartite Fc-FcR-antigen interactions can dramatically affect safety and efficacy
Case studies revealing overlooked effector functions, like ADNP and ADEP, in anti-CD20 mAbs
How SeromYx’s GCLP-certified platform enables antigen-specific Fc profiling at scale to support IND/BLA submissions

Speakers:

Silvia Crescioli, PhD., Independent Consultant:

Dr. Silvia Crescioli is an independent consultant and visiting Research Fellow at King’s College London, where she collaborates with the Cancer Antibody Discovery & Immunotherapy Group led by Prof. Sophia Karagiannis. She earned her PhD in Biomedical Sciences, Experimental Oncology, from the University of Florence in 2014, followed by eight years of postdoctoral research at King’s College London. Dr. Crescioli’s expertise lies in antibody therapeutics development for both cancer and noncancer indications, with a focus on cancer immunology, immunotherapy, antibody discovery, engineering, and glycoengineering. She is also a co-author on a recent publication in mAbs alongside SeromYx, highlighting her contributions to advancing the understanding of antibody effector functions.

Shashi Jatiani, PhD., Director of Research, SeromYx Systems:

Dr. Shashi Jatiani, Director of Research, leads internal R&D and external collaborations for the scientific development of the SeromYx Systems therapeutic antibody platform, driving clinical research and drug discovery in oncology, immuno-oncology, and autoimmunity. Shashi has a strong background in oncology and immunology, and over 18 years of research experience in both academic and biotech settings. He holds a Master of Science in Microbiology and a Doctorate in Molecular Biology from the Tata Institute for Fundamental Research, University of Mumbai.

Ian Wilkinson, PhD., CEO, GammaProteins :

Ian is a highly experienced executive manager with 20 years of experience in recombinant proteins. Following a PhD in structural biology and recombinant protein production, Ian held various positions in large-pharma on early stage research and discovery of antibody and other protein based biological drugs. He then moved to Absolute Antibody as its first employee and built the company into one of the global leaders for recombinant antibody sequencing, expression and engineering services as well as being the first antibody supplier to offer an extensive catalogue of entirely recombinant antibodies. Following a decade of being at the forefront of the recombinant revolution in the antibody RUO and IVD markets Ian now has his sights on disrupting the recombinant protein reagents market with Gamma Proteins.

Antibody Engineering & Therapeutics US 2024

Wed, 18 Jun 2025 20:50:53 GMT

Summary:

Antibody therapeutics are increasingly engineered with Fc modifications to fine-tune efficacy, extend half-life, or reduce effector function, but these changes come with risk. The complexity of Fc biology, combined with the interplay between Fab and Fc domains, means that intended outcomes don't always align with reality.

In this scientific briefing, Dr. Shashi Jatiani presents real-world examples where Fc engineering led to unexpected functional changes, despite rational design, and highlights how SeromYx’s high-throughput, antigen-specific Fc effector function platform can be used to detect, predict, and optimize antibody function across development stages.

Key takeaways include:

Why Fc function is more than receptor binding, it’s tripartite and context-dependent
Data showing how half-life extension mutations can reduce ADCC, ADNP, and NK cell activation
Novel functional profiling of anti-CD20 mAbs, revealing effector functions beyond ADCC and CDC
How SeromYx’s platform enables robust, scalable Fc characterization to support IND and BLA filings

Author:

Shashi Jatiani, PhD.

Festival of Biologics Europe 2024 Poster

Wed, 18 Jun 2025 20:48:30 GMT

Summary:

Anti-CD20 monoclonal antibodies are mainstays in the treatment of B-cell malignancies and autoimmune diseases, but how well do we understand the full spectrum of their immune mechanisms?

In this poster presented at Festival of Biologics 2024, SeromYx Systems leverages its high-throughput Fc effector function platform to comprehensively profile the functional landscape of rituximab, ofatumumab, and obinutuzumab. Using a full-length recombinant CD20 VLP from ACROBiosystems, the study confirms known mechanisms like ADCC, ADCP, and CDC, while also uncovering previously unreported effector functions such as eosinophil and neutrophil phagocytosis.

Key insights:

Biophysical FcγR and C1q binding strongly predicts functional outcomes
Clear differentiation in Fc profiles across clinically approved anti-CD20 mAbs
Novel functional findings may inform next-gen antibody engineering strategies

Author:

Shashi Jatiani, PhD.

Fc-Mediated Function Summit 2024

Wed, 18 Jun 2025 20:36:58 GMT

Summary:

Antibody therapeutics are increasingly engineered for specific Fc-mediated effector functions, but optimizing for safety and efficacy is more complex than it appears. In this presentation from the 2024 Fc-Mediated Function Summit, Dr. Lenny Moise explores how SeromYx’s industrialized, high-throughput platform enables comprehensive profiling of Fc effector functions, revealing unexpected tradeoffs and guiding smarter therapeutic design. Learn why functional characterization must go beyond affinity and subclass to capture the real-world impact of engineered antibodies.

Key Highlights:

Function doesn’t follow form: Engineering antibodies for enhanced or silenced Fc effector functions can unintentionally impact other functions, often unpredictably.
One Fab, many outcomes: Antibodies with identical Fab or Fc regions can still exhibit widely different effector profiles depending on target epitope and context.
Data that drives decisions: Early, multiplexed functional assessment across 15 Fc effector assays helps derisk lead candidate selection, streamline regulatory readiness, and ultimately improve clinical outcomes.

Author:

Lenny Moise, PhD.

The Fc-Mediated Effector Function Summit

Sun, 01 Jun 2025 04:59:50 GMT

The Fc-Mediated Effector Function Summit

Type: Conference

Dates: July 30th - 31st

Location: Boston, MA

The Fc-Mediated Effector Function Summit brings together leaders in immunology, antibody engineering, and translational science to discuss the latest advancements in Fc effector function. This focused event highlights emerging data, novel assay technologies, and strategies to optimize therapeutic antibody design for improved safety and efficacy.

mRNA-1273 and BNT162b2 COVID-19 vaccines elicit antibodies with differences in Fc-mediated effector functions

Sat, 31 May 2025 06:12:53 GMT

Authors: Kaplonek P, et al. Sci Transl Med. 2022 May 18;14(645):eabm2311.

Journal: Science Translational Medicine

Journal Abstract/ Summary:

The successful development of several coronavirus disease 2019 (COVID-19) vaccines has substantially reduced morbidity and mortality in regions of the world where the vaccines have been deployed. However, in the wake of the emergence of viral variants that are able to evade vaccine-induced neutralizing antibodies, real-world vaccine efficacy has begun to show differences across the two approved mRNA platforms, BNT162b2 and mRNA-1273; these findings suggest that subtle variation in immune responses induced by the BNT162b2 and mRNA-1273 vaccines may confer differential protection. Given our emerging appreciation for the importance of additional antibody functions beyond neutralization, we profiled the postboost binding and functional capacity of humoral immune responses induced by the BNT162b2 and mRNA-1273 vaccines in a cohort of hospital staff. Both vaccines induced robust humoral immune responses to wild-type severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and to variants of concern. However, differences emerged across epitope-specific responses, with higher concentrations of receptor binding domain (RBD)- and N-terminal domain-specific IgA observed in recipients of mRNA-1273. Antibodies eliciting neutrophil phagocytosis and natural killer cell activation were also increased in mRNA-1273 vaccine recipients as compared to BNT162b2 recipients. RBD-specific antibody depletion highlighted the different roles of non-RBD-specific antibody effector functions induced across the mRNA vaccines. These data provide insights into potential differences in protective immunity conferred by these vaccines.

Download PDF: https://pubmed.ncbi.nlm.nih.gov/35348368/

A replicating RNA vaccine confers protection against CrimeanCongo hemorrhagic fever in cynomolgus macaques

Sat, 31 May 2025 05:59:40 GMT

Background

Crimean-Congo hemorrhagic fever is a tick-borne febrile illness with wide geographic distribution. In recent years the geographic range of CCHFV and its tick vector have increased, placing an increasing number of people at risk of CCHFV infection. Currently there are no widely available vaccines and although the World Health Organization recommends ribavirin for treatment, its efficacy is unclear. Vaccines are critically needed for CCHFV.

Methods

Here we evaluated a promising replicating RNA vaccine for CCHFV in a Cynomolgus macaque model of disease.

Findings

In primed and boosted macaques, we found that our replicating RNA vaccine expressing the CCHFV nucleoprotein (repNP) was highly immunogenic, eliciting a robust non-neutralizing antibody response that conferred significant protection against CCHFV challenge. Macaques receiving a single repNP vaccination were partially protected against CCHFV challenge.

Interpretation

Our data demonstrate that our repNP vaccine and NP-specific antibody can protect against CCHFV in non-human primates.

Funding

This study was supported by the Intramural Research Program of the NIAID/NIH and the Medical CBRN Defense Consortium grant #MCDC2204-011.

Authors:

Hawman, David W. et al. eBioMedicine , Volume 115, 105698

Journal:

eBioMedicine

The importance of broadly measuring Fc mediated effector function early in the antibody development process

Mon, 12 May 2025 18:23:48 GMT

Journal Abstract:

The field of antibody therapeutics is rapidly growing, with over 210 antibodies currently approved or in regulatory review and ~ 1,250 antibodies in clinical development. Antibodies are highly versatile molecules that, with strategic design of their antigen-binding domain (Fab) and the domain responsible for mediating effector functions (Fc), can be used in a wide range of therapeutic indications. Building on many years of progress, the biopharmaceutical industry is now advancing innovative research and development by exploring new targets and new formats and using antibody engineering to fine-tune functions tailored to specific disease requirements. In addition to considering the target and the disease context, however, the unique features of each therapeutic antibody trigger a diverse set of Fc-mediated effector functions.

To avoid unexpected results on safety and efficacy outcomes during the later stages of the development process, it is crucial to measure the impact of antibody design on Fc-mediated effector function early in the antibody development process. Given the breadth of effector functions antibodies can deploy and the close interplay between the antibody Fab and Fc functional domains, it is important to conduct a comprehensive evaluation of Fc-mediated functions using an array of antigen-specific biophysical and cell-mediated functional assays. Here, we review antibody and Fc receptor properties that influence Fc effector functions and discuss their implications on development of safe and efficacious antibody therapeutics.

Authors:

Crescioli, S, Jatiani, S, & Moise, L, (2025). mAbs, 17(1).

Journal:

mAbs

Hyperinflammatory repolarisation of ovarian cancer patient macrophages by anti-tumour IgE antibody, MOv18, restricts an immunosuppressive macrophage:Treg cell interaction

Thu, 10 Apr 2025 16:27:23 GMT

Journal Abstract:

Ovarian cancer is the most lethal gynaecological cancer and treatment options remain limited. In a recent first-in-class Phase I trial, the monoclonal IgE antibody MOv18, specific for the tumour-associated antigen Folate Receptor-α, was well-tolerated and preliminary anti-tumoural activity observed. Pre-clinical studies identified macrophages as mediators of tumour restriction and pro-inflammatory activation by IgE. However, the mechanisms of IgE-mediated modulation of macrophages and downstream tumour immunity in human cancer remain unclear. Here we study macrophages from patients with epithelial ovarian cancers naive to IgE therapy. High-dimensional flow cytometry and RNA-seq demonstrate immunosuppressive, FcεR-expressing macrophage phenotypes. Ex vivo co-cultures and RNA-seq interaction analyses reveal immunosuppressive associations between patient-derived macrophages and regulatory T (Treg) cells. MOv18 IgE-engaged patient-derived macrophages undergo pro-inflammatory repolarisation ex vivo and display induction of a hyperinflammatory, T cell-stimulatory subset. IgE reverses macrophage-promoted Treg cell induction to increase CD8+ T cell expansion, a signature associated with improved patient prognosis. On-treatment tumours from the MOv18 IgE Phase I trial show evidence of this IgE-driven immune signature, with increased CD68+ and CD3+ cell infiltration. We demonstrate that IgE induces hyperinflammatory repolarised states of patient-derived macrophages to inhibit Treg cell immunosuppression. These processes may collectively promote immune activation in ovarian cancer patients receiving IgE therapy.

Authors:

Osborn, G., López-Abente, J., Adams, R. et al.

Journal:

Nature Communications

Advancing Therapeutic IgE – Collaborative Discovery of MOv18's Mechanism in Ovarian Cancer

Thu, 10 Apr 2025 13:38:39 GMT

SUMMARY:

Ovarian cancer is the most lethal gynecological malignancy, with limited treatment options and a profoundly immunosuppressive tumor microenvironment (TME). Tumor-associated macrophages(TAMs) are abundant in ovarian tumors and ascites, where they play a major role in suppressing anti-tumor T cell responses.

In this collaborative study with King’s College London, researchers explored a first-in-class IgE

monoclonal antibody (mAb), MOv18 IgE, targeting Folate Receptor- α (FR α ), and investigated how it reshapes macrophage behavior and T cell interactions, using Seromyx's profiling tools to uncover previously uncharacterized Fc effector mechanisms.

IN COLLABORATION WITH:

King's College London - Karagiannis Lab

Study Shows How New Antibody Therapy Works Against Ovarian Cancer

Thu, 10 Apr 2025 05:00:00 GMT

Research has shed light on how a new type of antibody treatment reactivates patients’ immune cells to fight ovarian cancer. The research, from the group of Professor Sophia Karagiannis at King’s College London, could help to better understand the responses of patients who receive this type of therapy.

SeromYx Systems, Inc. Appoints Andrew Ball, PhD, as Chief Executive Officer

Wed, 05 Feb 2025 16:26:00 GMT

Woburn, MA, February 5th, 2025 — SeromYx Systems, Inc., a global leader in high-throughput antibody characterization and Systems Serology services, today announced the retirement of Chief Executive Officer, Mr. Piers Whitehead, a co-founder of the company,...

Application Note│Comprehensive Profiling of Approved Anti-CD20 mAbs Using Fc Effector Function Platform

Tue, 08 Oct 2024 12:01:00 GMT

Woburn, MA / Newark, DE – October 1st, 2024 - SeromYx Systems, a cutting-edge immunology technology company, and ACROBiosystems, a leading provider for life science solutions and tools, are excited to announce the release of their joint study on the...

Comprehensive Profiling of Approved Anti-CD20 mAbs Using Fc Effector Function Platform

Tue, 01 Oct 2024 18:44:29 GMT

Summary:

This study offers significant insights into the profiling of approved anti-CD20 monoclonal antibodies (mAbs) using the SeromYx Fc effector function platform. By employing high-quality, full-length human CD20 virus-like particles (VLPs) from ACROBiosystems, we achieved a physiologically relevant assessment of antibody binding and effector functions. This enabled a detailed comparison between Type I (Rituximab and Ofatumumab) and Type II (Obinutuzumab) anti-CD20 mAbs, revealing distinct binding profiles and effector function capabilities. Our findings indicated that Type I mAbs demonstrated stronger binding to CD20-VLPs (Virus-like particles) and to Fc receptors in the presence of antigen compared to the Type II mAb, highlighting how structural differences could influence their mechanisms of action.

We observed an overall correlation between biophysical tripartite binding assays and effector cell function assays, validating the predictive utility of tripartite binding assays for mAb effector functions. Importantly, the discovery of robust antibody-dependent neutrophil phagocytosis (ADNP) and eosinophil phagocytosis (ADEP) activities for anti-CD20 mAbs significantly broadens our understanding of their potential in vivo mechanisms. These findings suggest that the involvement of neutrophils and eosinophils could impact the efficacy and safety of these mAbs in diverse disease states and tissue environments. Additionally, the differentiation between Type I and Type II mAbs across multiple assays underscores the importance of these distinctions in therapeutic applications and next generation antibody design.

In conclusion, broadly profiling Fc effector function using the SeromYx Fc effector function platform not only recapitulated the known Fc effector functions of anti-CD20 mAbs but also uncovered novel potential mechanisms of action. These insights have substantial implications for optimizing current anti-CD20 therapies and developing new, more effective mAbs. Furthermore, the CD20-VLP system presents an opportunity to design and characterize mAbs with tailored effector function profiles for specific therapeutic applications, potentially leading to more personalized and effective treatments for a variety of diseases.

Authors:

P. Hsueh, M. Friedman, S. Jatiani (2024)

SeromYx Systems and ACROBiosystems Announces Strategic Collaboration on Comprehensive Functional Profiling of Anti-CD20 Monoclonal Antibodies

Tue, 01 Oct 2024 15:34:00 GMT

SeromYx Systems Announces Strategic Collaboration to Advance Understanding and Treatment of Long COVID

Wed, 25 Sep 2024 14:32:00 GMT

Woburn, MA, September, 25th, 2024 – SeromYx Systems, a leading provider of GCLP Systems Serology and Antibody characterization services, is excited to announce a new immunobiology collaboration to better understand Post-Acute Sequelae of SARS-CoV-2...

White Paper │ View from the Fc: 5 Rules for mAb Development Risk Reduction

Wed, 07 Aug 2024 12:00:00 GMT

View from the Fc: Five Rules for mAb Development Risk Reduction

Thu, 01 Aug 2024 18:54:35 GMT

Summary:

Designing monoclonal antibodies and related modalities such as ADCs and bispecifics with appropriate Fc function is critical to product safety and efficacy, but fiendishly hard. Outcomes are contextual, meaning that what works in one disease state/epitope setting may not hold in another, so the “rules” keep changing. And the factors driving Fc function are strongly interrelated, meaning that changes with one intent often have unexpected and undesirable consequences elsewhere. SeromYx offers the broadest and robust platform for Fc functional characterization.

Where does our platform fit in? We provide a unique resource for antibody discovery and development with an industrial quality system. While we add value throughout the mAb discovery and development process, from pre-IND to BLA enabling, we encourage developers to utilize our capabilities earlier so that the best candidates can be identified and nominated for the clinic. By measuring outcomes in a robust way, we offer a distinct advantage to developers so that they can maximize the rewards of approvals and minimize the risk of clinical failures due to underexploited and/or incompletely characterized Fc biology.

WEBINAR | Strategies for Mitigating the Unpredictability of Fc-Mediated Functions in Antibody Development

Thu, 09 Nov 2023 17:40:20 GMT

Background:

Optimization of Fc function can lead to the development of safer and more efficacious therapeutic antibody products, but analyses of Fc function may be underexploited in the antibody design process. We introduce a high-throughput platform for antigen-specific testing of Fc effector activities, empowering enhanced hit-to-lead screening in early stages of antibody development for the treatment of cancer, autoimmunity, neurodegeneration, and infectious diseases.

Speaker:

Dr. Lenny Moise, VP Research, oversees the scientific development of the SeromYx Systems Serology platform, driving clinical research and drug discovery in infectious disease, immuno-oncology, autoimmunity, and neurology. Previously, as Director of Vaccine Research at EpiVax, he harnessed immunoinformatics to design innovative vaccines leveraging T cell immunity for viral and bacterial infectious diseases and cancer. Over that time, he studied T cell responses to vaccines and developed immunoinformatic tools as a faculty member at the Institute for Immunology and Informatics (University of Rhode Island) and the Center for Vaccines and Immunology (University of Georgia). Lenny trained in structure-function analysis of snake toxin-ion channel interactions using structural, biochemical, and electrophysiological methods and holds a Bachelor of Science and a doctorate from Brown University.

Fc-mediated functions of nirsevimab complement direct respiratory syncytial virus neutralization but are not required for optimal prophylactic protection

Tue, 10 Oct 2023 12:32:01 GMT

Introduction:

Nirsevimab is an extended half-life (M252Y/S254T/T256E [YTE]-modified) monoclonal antibody to the pre-fusion conformation of the respiratory syncytial virus (RSV) Fusion protein, with established efficacy in preventing RSV-associated lower respiratory tract infection in infants for the duration of a typical RSV season. Previous studies suggest that nirsevimab confers protection via direct virus neutralization. Here we use preclinical models to explore whether fragment crystallizable (Fc)-mediated effector functions contribute to nirsevimab-mediated protection.

Methods:

Nirsevimab, MEDI8897* (i.e., nirsevimab without the YTE modification), and MEDI8897*-TM (i.e., MEDI8897* without Fc effector functions) binding to Fc γ receptors (FcγRs) was evaluated using surface plasmon resonance. Antibody-dependent neutrophil phagocytosis (ADNP), antibody-dependent cellular phagocytosis (ADCP), antibody-dependent complement deposition (ADCD), and antibody-dependent cellular cytotoxicity (ADCC) were assessed through in vitro and ex vivo serological analyses. A cotton rat challenge study was performed with MEDI8897* and MEDI8897*-TM to explore whether Fc effector functions contribute to protection from RSV.

Results:

Nirsevimab and MEDI8897* exhibited binding to a range of FcγRs, with expected reductions in FcγR binding affinities observed for MEDI8897*-TM. Nirsevimab exhibited in vitro ADNP, ADCP, ADCD, and ADCC activity above background levels, and similar ADNP, ADCP, and ADCD activity to palivizumab. Nirsevimab administration increased ex vivo ADNP, ADCP, and ADCD activity in participant serum from the MELODY study (NCT03979313). However, ADCC levels remained similar between nirsevimab and placebo. MEDI8897* and MEDI8897*-TM exhibited similar dose-dependent reduction in lung and nasal turbinate RSV titers in the cotton rat model.

Conclusion:

Nirsevimab possesses Fc effector activity comparable with the current standard of care, palivizumab. However, despite possessing the capacity for Fc effector activity, data from RSV challenge experiments illustrate that nirsevimab-mediated protection is primarily dependent on direct virus neutralization.

Authors:

Brady, Tyler et al. Frontiers in Immunology , Volume 14, 1283120.

Journal:

Frontiers in Immunology

Assay Development, Qualification, and Validation: Supporting Vaccine Trials with Robust Functional Antibody Testing

Sun, 12 Jun 2022 15:46:02 GMT

Summary:

As the therapeutic antibody landscape evolves, the ability to accurately measure extra-neutralizing functions, such as ADCC, ADCP, and complement activation , has become critical for candidate selection, MOA characterization, and regulatory submissions. This case study from SeromYx outlines the formal development and GCLP qualification of a SARS-CoV-2–specific functional assay , offering a model for how Systems Serology assays can be adapted and validated to meet the rigorous demands of late-stage development.

Journal: Nature Reviews Immunology

Journal Abstract/ Summary: Antibodies play an essential role in host defence against pathogens by recognizing microorganisms or infected cells. Although preventing pathogen entry is one potential mechanism of protection, antibodies can control and eradicate infections through a variety of other mechanisms. In addition to binding and directly neutralizing pathogens, antibodies drive the clearance of bacteria, viruses, fungi and parasites via their interaction with the innate and adaptive immune systems, leveraging a remarkable diversity of antimicrobial processes locked within our immune system. Specifically, antibodies collaboratively form immune complexes that drive sequestration and uptake of pathogens, clear toxins, eliminate infected cells, increase antigen presentation and regulate inflammation. The diverse effector functions that are deployed by antibodies are dynamically regulated via differential modification of the antibody constant domain, which provides specific instructions to the immune system. Here, we review mechanisms by which antibody effector functions contribute to the balance between microbial clearance and pathology and discuss tractable lessons that may guide rational vaccine and therapeutic design to target gaps in our infectious disease armamentarium.

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Systems serology for evaluation of HIV vaccine trials

Mon, 30 Jan 2017 16:38:58 GMT

Authors: Ackerman ME, Barouch DH, Alter G. Systems serology for evaluation of HIV vaccine trials. Immunol Rev. 2017 Jan;275(1):262-270. doi: 10.1111/imr.12503. PMID: 28133810; PMCID: PMC5292205.

Journal: Immunological Reviews

Journal Abstract/ Summary: The scale and scope of the global epidemic, coupled to challenges with traditional vaccine development approaches, point toward a need for novel methodologies for HIV vaccine research. While the development of vaccines able to induce broadly neutralizing antibodies remains the ultimate goal, to date, vaccines continue to fail to induce these rare humoral immune responses. Conversely, growing evidence across vaccine platforms in both non-human primates and humans points to a role for polyclonal vaccine-induced antibody responses in protection from infection. These candidate vaccines, despite employing disparate viral vectors and immunization strategies, consistently identify a role for functional or non-traditional antibody activities as correlates of immunity. However, the precise mechanism(s) of action of these “binding” antibodies, their specific characteristics, and their ability to be selectively induced and/or potentiated to result in complete protection merits parallel investigation to neutralizing antibody-based vaccine design approaches. Ultimately, while neutralizing and functional antibody-based vaccine strategies need not be mutually exclusive, defining the specific characteristics of “protective” functional antibodies may provide a target immune profile to potentially induce more robust immunity against HIV. Specifically, one approach to guide the development of functional antibody-based vaccine strategies, termed “systems serology”, offers an unbiased and comprehensive approach to systematically survey humoral immune responses, capturing the array of functions and humoral response characteristics that may be induced following vaccination with high resolution. Coupled to machine learning tools, large datasets that explore the “antibody-ome” offer a means to step back from anticipated correlates and mechanisms of protection and toward a more fundamental understanding of coordinated aspects of humoral immune responses, to more globally differentiate among vaccine candidates, and most critically, to identify the features of humoral immunity that distinguish protective from non-protective responses. Overall, the systematic serological approach described here aimed at broadly capturing the enormous biodiversity in antibody profiles that may emerge following vaccination, complements the existing cutting edge tools in the cellular immunology space that survey vaccine-induced polyfunctional cellular activity by flow cytometry, transcriptional profiling, epigenetic, and metabolomic analysis to offer a means to develop both a more nuanced and a more complete understanding of correlates of protection to support the design of functional vaccine strategies.

Download PDF: https://onlinelibrary.wiley.com/doi/10.1111/imr.12503

A Functional Role for Antibodies in Tuberculosis

Thu, 06 Oct 2016 17:20:42 GMT

Authors: Lu, Lenette L. et al. Cell, Volume 167, Issue 2, 433 - 443.e14

Journal: Cell Press

Journal Abstract/ Summary: While a third of the world carries the burden of tuberculosis, disease control has been hindered by a lack of tools, including a rapid, point-of-care diagnostic and a protective vaccine. In many infectious diseases, antibodies (Abs) are powerful biomarkers and important immune mediators. However, in Mycobacterium tuberculosis (Mtb) infection, a discriminatory or protective role for humoral immunity remains unclear. Using an unbiased antibody profiling approach, we show that individuals with latent tuberculosis infection (Ltb) and active tuberculosis disease (Atb) have distinct Mtb-specific humoral responses, such that Ltb infection is associated with unique Ab Fc functional profiles, selective binding to FcγRIII, and distinct Ab glycosylation patterns. Moreover, compared to Abs from Atb, Abs from Ltb drove enhanced phagolysosomal maturation, inflammasome activation, and, most importantly, macrophage killing of intracellular Mtb. Combined, these data point to a potential role for Fc-mediated Ab effector functions, tuned via differential glycosylation, in Mtb control.

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Dissecting Polyclonal Vaccine-Induced Humoral Immunity against HIV Using Systems Serology

Thu, 05 Nov 2015 17:18:08 GMT

Authors: Chung, Amy W. et al. Cell, Volume 163, Issue 4, 988 - 998

Journal: Cell

Journal Abstract/ Summary: While antibody titers and neutralization are considered the gold standard for the selection of successful vaccines, these parameters are often inadequate predictors of protective immunity. As antibodies mediate an array of extra-neutralizing Fc functions, when neutralization fails to predict protection, investigating Fc-mediated activity may help identify immunological correlates and mechanism(s) of humoral protection. Here, we used an integrative approach termed Systems Serology to analyze relationships among humoral responses elicited in four HIV vaccine trials. Each vaccine regimen induced a unique humoral “Fc fingerprint.” Moreover, analysis of case:control data from the first moderately protective HIV vaccine trial, RV144, pointed to mechanistic insights into immune complex composition that may underlie protective immunity to HIV. Thus, multi-dimensional relational comparisons of vaccine humoral fingerprints offer a unique approach for the evaluation and design of novel vaccines against pathogens for which correlates of protection remain elusive.

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Protective efficacy of adenovirus/protein vaccines against SIV challenges in rhesus monkeys

Thu, 02 Jul 2015 16:52:09 GMT

Authors: Dan H. Barouch et al. ,Protective efficacy of adenovirus/protein vaccines against SIV challenges in rhesus monkeys.Science 349 ,320-324(2015).DOI: 10.1126/science.aab3886

Journal: Science

Journal Abstract/ Summary: Preclinical studies of viral vector–based HIV-1 vaccine candidates have previously shown partial protection against neutralization-resistant virus challenges in rhesus monkeys. In this study, we evaluated the protective efficacy of adenovirus serotype 26 (Ad26) vector priming followed by purified envelope (Env) glycoprotein boosting. Rhesus monkeys primed with Ad26 vectors expressing SIVsmE543 Env, Gag, and Pol and boosted with AS01B-adjuvanted SIVmac32H Env gp140 demonstrated complete protection in 50% of vaccinated animals against a series of repeated, heterologous, intrarectal SIVmac251 challenges that infected all controls. Protective efficacy correlated with the functionality of Env-specific antibody responses. Comparable protection was also observed with a similar Ad/Env vaccine against repeated, heterologous, intrarectal SHIV-SF162P3 challenges. These data demonstrate robust protection by Ad/Env vaccines against acquisition of neutralization-resistant virus challenges in rhesus monkeys.

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Polyfunctional Fc-Effector Profiles Mediated by IgG Subclass Selection Distinguish RV144 and VAX003 Vaccines

Wed, 19 Mar 2014 17:15:14 GMT

Authors: Amy W. Chung et al. ,Polyfunctional Fc-Effector Profiles Mediated by IgG Subclass Selection Distinguish RV144 and VAX003 Vaccines.Sci. Transl. Med. 6 ,228ra38-228ra38(2014).DOI: 10.1126/scitranslmed.3007736

Journal: Science Translational Medicine

Journal Abstract/ Summary: The human phase 2B RV144 ALVAC-HIV vCP1521/AIDSVAX B/E vaccine trial, held in Thailand, resulted in an estimated 31.2% efficacy against HIV infection. By contrast, vaccination with VAX003 (consisting of only AIDSVAX B/E) was not protective. Because protection within RV144 was observed in the absence of neutralizing antibody activity or cytotoxic T cell responses, we speculated that the specificity or qualitative differences in Fc-effector profiles of nonneutralizing antibodies may have accounted for the efficacy differences observed between the two trials. We show that the RV144 regimen elicited nonneutralizing antibodies with highly coordinated Fc-mediated effector responses through the selective induction of highly functional immunoglobulin G3 (IgG3). By contrast, VAX003 elicited monofunctional antibody responses influenced by IgG4 selection, which was promoted by repeated AIDSVAX B/E protein boosts. Moreover, only RV144 induced IgG1 and IgG3 antibodies targeting the crown of the HIV envelope V2 loop, albeit with limited coverage of breakthrough viral sequences. These data suggest that subclass selection differences associated with coordinated humoral functional responses targeting strain-specific protective V2 loop epitopes may underlie differences in vaccine efficacy observed between these two vaccine trials.

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SeromYx

Biointron & Kactus Lunch & Learn: Antibody Series III

Type: Lunch & Learn

Date: May 8th, 2026 @ 11:30am

Location: Boston, MA

Biointron & Kactus Lunch & Learn: Antibody Series III

PEGS Boston

Type: Conference

Dates: May 11th-15th, 2026

Location: Boston, MA

PEGS Boston 2026

Presentation

Title: Optimizing Therapeutic Antibodies by Balancing the Safety and Efficacy of Their Fc-Mediated Effector Functions

Date: May 14th, 2026 at 3:40pm

Speaker: Amanda Gross, PhD., Associate Director, Immunology

Glycan pairing in therapeutic IgG orchestrates Fcγ receptor engagement and ADCC: an integrated structure-function approach for thorough evaluation of Fc N-glycans as critical quality attributes

The Fc Review:

Are we oversimplifying Fc glycosylation?

Background:

The study highlights:

Implications for antibody development:

Our perspective:

References:

World Vaccine Congress US 2026

Moving Beyond Binding: Why Antibody Function Matters for Vaccine Efficacy

NextGen Biomed Workshop 2026

Summary:

Impacts of Antibody Structure and Mixtures on Receptor Signaling for Antibody-Dependent Cellular Cytotoxicity

The Fc Review:

How do antibody structure and binding dynamics shape ADCC signaling?

Background:

The study highlights:

Implications for antibody development:

Our perspective:

References:

Cross-species cellular mapping and humanization of Fcγ receptors to advance antibody modeling

The Fc Review:

How well do our preclinical models capture human Fc biology?

Background:

The study highlights:

Implications for antibody development:

Our perspective:

References:

Fc engineering by monoclonal mammalian cell display for improved affinity and selectivity towards FcγRs

The Fc Review:

How are antibody developers actually using Fc engineering today?

Background:

The review highlights:

Implications for antibody development:

Our perspective:

References:

Antibody Engineering & Therapeutics US 2025

Background:

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Generative design of antibody Fc-variants with synthetic and programmable functional profiles

The Fc Review:

Can we program the Fc region?

Background:

The authors highlight:

Implications:

How do we evaluate Fc behavior when relevant biology spans multiple immune pathways?

Our perspective:

Human IgG Fc-engineering for enhanced plasma half-life, mucosal distribution and killing of cancer cells and bacteria

The Fc Review:

One Fc variant, three advantages?

Background:

The review highlights:

Implications:

Our perspective:

Want to catch up on previous entries in The Fc Review?

SITC Poster 2025

Background:

Objective:

Methods:

Results:

Conclusion:

Authors:

Design and engineering of bispecific antibodies: insights and practical considerations

The Fc Review:

How does Fc engineering shape bispecific antibody function?