2026/05/01 by Pradip Bajgain, Yang Feng, Mariela Puebla +18 · 1 voice
Immunology and Microbiology · Medicine · #CAR-T cell therapy research #Immunotherapy and Immune Responses #Monoclonal and Polyclonal Antibodies Research
paper · doi:10.1016/j.xcrm.2026.102782
openalex publication_date 2026/05/01 · openalex created_date 2026/05/02 · openalex updated_date 2026/07/22
B7-H3 is a cell surface protein overexpressed in many solid tumors and an attractive target for chimeric antigen receptor (CAR) T cell therapy. The most clinically advanced B7-H3 CARs derive from murine monoclonal antibodies (mAbs) 376.96 and MGA271 and are now in phase 1/2 trials. However, non-human mAb sequences can provoke immune responses, leading to CAR T cell rejection and therapeutic failure. Although single-chain variable fragment (scFv) humanization reduces this risk, residual foreign residues within variable domains remain. To overcome this limitation, here we use in vitro phage display to generate fully human B7-H3-specific scFvs for CAR design. In pancreatic cancer, neuroblastoma, and glioblastoma xenograft models, CAR T cells incorporating the lead human binder Y111 are well tolerated and demonstrate superior antitumor activity compared with 376.96- and MGA271-based CARs. Y111 CAR treatment induces complete responses, tumor rejection, and significant survival benefits, identifying Y111 as a promising fully human B7-H3 CAR for solid tumors.