Towards optimizing cancer immunotherapeutic index: anti-CD3e Mono-Fab, a novel T cell-based therapeutic approach with less auto-Immunogenic profile.

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Presentation Time: 02:15 PM - 03:30 PM
Poster Board Number: B216
Abstract ID: 5317

Presenting Author:
Onyekachi J Okpasuo , PhD Student (Graduate Research Assistant) at Univ. of Missouri, Columbia

Abstract:

Despite advancement of cancer therapeutic approaches with immune checkpoint inhibitors (ICIs) against several tumor types, its anti-tumor benefit is limited by the emergence of immune related adverse events (irAEs). irAEs with an autoimmune phenotype, show a wide spectrum of toxicities that affect almost all organ systems. Several studies suggest a positive correlation between irAEs and anti-tumor response, with higher levels of toxicities seen with combination therapies. Finding strategies that optimize efficacy with less toxicity has been in the frontline of immunotherapy. We have shown a novel therapeutic strategy: anti-CD3e Monovalent Fab fragment (Mono-Fab) that targets the TCR/CD3 complex, strengthening signaling response to moderately weak antigens. Anti-CD3e Mono-Fab as a single therapy and in synergy with combination ICIs is effective against metastatic melanomas. To determine its optimal therapeutic index, we utilized a cell mediated experimental autoimmune encephalomyelitis mouse model as a platform to gauge potential to cause irAEs in the clinic. In this model, anti-CTLA-4 mAb administration to mice increases severity of their EAE symptoms over those observed in mice treated with appropriate IgG control, while anti-CD3e mono-Fab treatment does not. Thus, Anti-CD3e Mono-Fab contrast as an efficient potentially non-toxic cancer immunotherapy when compared with anti-CTLA-4 antibodies that are known to cause irAEs in patients.