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Innovative Research in T cell Biology and Cancer Immunology

T cells have the unique capacity to specifically detect and selectively destroy cancer cells based on T cell receptor-driven recognition of tumor antigens. All therapeutic approaches that have shown efficacy in the clinic are fundamentally based on enhancing the function of cytotoxic T cells. The Wucherpfennig lab aims to develop the next generation of cancer immunotherapies by in-depth mechanistic studies that identify the critical molecular switches controlling the ability of T cells to destroy cancers in highly immunosuppressive tumor microenvironments.

We recently reported a novel in vivo approach that enables discovery of negative regulators of T cell function in tumors. The genes we discovered provide exciting opportunities to mechanistically understand key regulatory mechanisms in T cells. Furthermore, they provide an opportunity to enhance the anti-tumor activity of adoptive T cell therapies, for example with T cells that express a chimeric antigen receptor (CAR).

We have also developed novel approaches to investigate immune responses in patients responding to cancer immunotherapies. A subset of patients generates antibodies against immunosuppressive molecules, and we developed a technique for isolation of memory B cells that produce such antibodies. A single cell PCR procedure provides the sequences of the antibody heavy and light chain genes, enabling production of recombinant antibodies for in depth mechanistic studies. We have found that such patient-derived antibodies can have intriguing functional properties and strong anti-tumor activity in humanized mouse models. This approach thereby enables us to directly learn from patients who respond to cancer immunotherapies and to develop human therapeutic antibodies.