The novel CD16A/anti-CD3 bifunctional protein, eCD16A/anti-CD3-BFP, redirects T cell cytotoxicity toward antibody-bound target cells - PubMed
6 hours ago
- #T cell engager
- #cancer immunotherapy
- #bispecific antibody
- Researchers developed eCD16A/anti-CD3-BFP, a bifunctional protein that combines the high-affinity CD16A extracellular domain (binds IgG1 Fc) with an anti-CD3 scFv to redirect T cell cytotoxicity toward antibody-bound targets.
- In combination with therapeutic IgG1 antibodies (e.g., rituximab, cetuximab, trastuzumab, anti-PD-L1), eCD16A/anti-CD3-BFP induced specific killing of antigen-expressing tumor cells in vitro, ex vivo, and in mouse xenograft models.
- Ex vivo, eCD16A/anti-CD3-BFP plus rituximab eliminated B cells in human peripheral blood samples; efficacy was enhanced by adding γ9δ2 T cells (autologous or allogeneic).
- Serum immunoglobulins interfered with activity, but this could be overcome by dose escalation or using Fc-glycoengineered antibodies (e.g., glycoengineered rituximab).
- The adapter also worked with anti-Epstein-Barr virus (EBV) antibodies to direct T cell cytotoxicity against EBV-infected cells, supporting its potential as a broad anti-cancer therapeutic engaging both innate and adaptive immunity.