Anti-CD3e Fab fragments enrich T cell functional effectors and promote varied TCR clones to boost anti-tumor activity 4677

Abstract Description Previously, we showed that anti-CD3ε monovalent Fab fragments (Mono-Fabs) enhance T cell responses to poorly immunogenic antigens without activating antigen-unengaged T cells or disrupting responses to cognate antigens, producing “T cell co-potentiation”. This effect can be exploited as a novel immunotherapeutic principle by enhancing the capacity of T cells to control tumor progression, as observed in B6 mice implanted intravenously with the syngeneic melanoma B16F10. Now using additional B6 syngeneic melanoma cell lines, the YUMM/ER1.7, varying on their load of passenger mutations induced after UV exposure, we report a direct relationship between TAAs availability in the melanoma lines tested and anti-tumor effects of Anti-CD3ε Mono-Fabs observed, that appears linked to higher frequencies of effector T cell subpopulations and variety of T cell clones found in mice displaying positive anti-tumor responses, and requires intact CXXC motifs in CD3ε extracellular domains to expose a cytoplasmic proline rich sequence (PRS) in CD3ε. Funding Sources MU Start-up funds, NIAID R01 AI097187, NCI U01CA244314 Topic Categories Tumor Immunology: Checkpoints, Prevention, and Treatment (TIPT)