Seminars

Alloreactive T cells drive acute transplant rejection by reacting against peptides displayed on non-self MHC, or allo-MHC. Despite the critical role of alloreactivity in causing transplant rejection, the molecular basis of T cell allorecognition of peptide-allo-MHC complexes remains poorly understood. We are applying high-throughput sequencing and antigen profiling tools to elucidate the recognition patterns and antigen targets of alloreactive T cells, which may offer novel means to track and treat alloresponses driving graft rejection.

Tumor infiltrating lymphocyte (TIL) therapy harvests patient tumor-reactive T cells and massively expands them ex vivo for reinfusion. This approach has led to the first FDA-approved immune cell therapy against solid tumors. However, TIL therapy is limited by a lengthy and costly ex vivo manufacturing pipeline. Therefore, directly engineering tumor antigen-specific T cells in vivo is a promising approach to democratize TIL therapy for patients. Here, we demonstrate selective engineering of primary human antigen-specific T cells ex vivo using targeted lentiviral vectors and aim to achieve antigen-specific gene delivery in vivo.