NextGen Biomed 2025

June 18, 2025

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.

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

February 12, 2026
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. 

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

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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

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

December 4, 2025
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. 

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

November 20, 2025
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?

Design and engineering of bispecific antibodies: insights and practical considerations

October 28, 2025
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

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

October 23, 2025
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.
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Antibody Engineering and Therapeutics 2025

October 10, 2025
Antibody Engineering & Therapeutics 2025

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

September 15, 2025
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.

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

September 9, 2025
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.

NextGen Biomed 2026

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