Generation of effective and specific human TCRs against tumor/testis antigen NY-ESO-1 in mice with humanized T cell recognition system.

ABSTRACT: Generation of high avidity T cell receptors (TCRs) reactive to tumor-associated antigens (TAA) is impaired by tolerance mechanisms, which is an obstacle to effective T cell therapies for cancer treatment. NY-ESO-1, a human cancer-testis antigen, represents an attractive target for such therapies due to its broad expression in different cancer types and the restricted expression in normal tissues. Utilizing transgenic mice with a diverse human TCR repertoire, we isolated effective TCRs against NY-ESO-1_157-165 restricted to HLA-A*02:01. We compared the functions of the murine-derived TCR with human-derived TCRs and an affinity matured TCR, using in vitro co-culture and in vivo adoptive T cell transfer in tumor-bearing mice. Alanine scan, x-scan, LCL assay were employ

SUBMITTER: Chen XT 

PROVIDER: S-EPMC11703889 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature