Preclinical model for evaluating human TCRs against chimeric syngeneic tumors.

Background: The adoptive cell transfer (ACT) of T cell receptor (TCR)-engineered T cells targeting the HLA-A2-restricted epitope NY-ESO-1 (A2/NY) has yielded important clinical responses against several cancers. A variety of approaches are being taken to augment tumor control by ACT including TCR affinity-optimization and T-cell coengineering strategies to address the suppressive tumor microenvironment (TME). Most TCRs of clinical interest are evaluated in immunocompromised mice to enable human T-cell engraftment and do not recapitulate the dynamic interplay that occurs with endogenous immunity in a treated patient.