Fc-mediated Function Summit 2025
August 7, 2025
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.
Authors:
Shashi Jatiani, PhD.
Antibody Engineering & Therapeutics 2025
The World Vaccine Congress Europe 2025
Festival of Biologics
The Fc-Mediated Effector Function Summit
Authors: Kaplonek P, et al. Sci Transl Med. 2022 May 18;14(645):eabm2311.
Authors: Hawman, David W. et al. eBioMedicine, Volume 115, 105698
Authors: Crescioli, S, Jatiani, S, & Moise, L, (2025). mAbs, 17(1). Journal: mAbs
Authors: Osborn, G., López-Abente, J., Adams, R. et al.
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...
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 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)
