Integrated Platforms for the Preclinical Evaluation of T-Cell Engagers

T-cell engagers (TCEs), bispecific antibodies that simultaneously target the T-cell surface marker CD3 and a tumor-associated antigen (TAA), have emerged as promising cancer therapeutics. However, their complex mechanisms of action necessitate physiologically relevant models to accurately assess efficacy and safety in the preclinical stage. GemPharmatech established a suite of medium- to high-throughput in vitro assays to screen TCE candidates based on target binding, T-cell activation, and tumor cell killing. Lead molecules were further evaluated in in vivo efficacy studies using both xenograft and syngeneic models. For xenograft studies, we employed NCG and NCG-MHC-dKO mice. The NCG-MHC-dKO model, generated by knocking out murine MHC class I and II genes in the immunodeficient NCG background, minimizes graft-versus-host disease (GvHD) following human PBMC engraftment, thus extending the study window. Our integrated in vitro screening systems and in vivo models—including NCG, NCG-MHC-dKO, and CD3-humanized mouse strains—enable rapid, scalable, and translational evaluation of T-cell engager candidates, providing a robust platform to accelerate immuno-oncology drug development.