Systems serology: profiling vaccine induced humoral immunity against HIV

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. 

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 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

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.

Antibody Engineering & Therapeutics 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.

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

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.