Application Note│Comprehensive Profiling of Approved Anti-CD20 mAbs Using Fc Effector Function Platform
Abigail Harris • October 8, 2024
Summary
CD20 is a key target for treating B-cell malignancies, enabling selective B-cell depletion. This study compared Rituximab (RTX), Ofatumumab (OFA), and Obinutuzumab (OBZ), revealing distinct profiles of known and previously unreported Fc-effector functions, offering insights into mechanisms of antibody efficacy and safety.
This study uses the advanced SeromYx Fc-effector function platform to profile marketed anti-CD20 mAbs, comparing their biophysical binding and cellular Fc functions by leveraging a well-characterized recombinant human full-length CD20-VLPs from ACROBiosystems, aiming to deepen understanding of their potential mechanisms of action and clinical implications.
Key Findings
- Biophysical binding assays are predictive of Fc-driven cellular functions
- SeromYx’s platform recapitulates known Fc effector functions of marketed anti-CD20 mAbs
- Identification of previously unreported effector functions may guidedevelopment of improved CD20 mAbs
Authors: Stefanutti E, Ramani R, Whitener B, Dang H, Bélanger S, Somasundaram L, Cortina K, De Marco A, Tam T, Chai Q, Cameroni E, Gupta R, Schmid MA, Miller JL, Zumsteg AB, Purcell LA, Drewry LL. 0. Analysis of Fc-dependent effector functions of anti-malaria circumsporozoite protein antibodies. Microbiol Spectr 0:e00863-25. Journal: Microbiology Spectrum
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.
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)
