The Christopher Klebanoff Lab

A form of cancer immunotherapy termed adoptive T cell transfer (ACT), in which a patient’s own T cells are engineered to recognize and attack cancer cells, can induce durable complete remissions in patients with advanced hematologic malignancies. By contrast, a similar approach has thus far failed to work in most patients with solid malignancies, the leading cause of adult cancer-related deaths. Two critical gaps in knowledge have limited the ability of ACT to be successfully applied to solid cancers: 1) understanding which antigens on the surface of cancer cells can be targeted by T cells that do not have the potential to cross- react with and injure normal tissues, and 2) insight into what factor(s) restrain the ability of transferred T cells to infiltrate, expand, and persist within a solid tumor mass. Using diverse techniques, including single-cell sequencing, biophysical measurements of T cell receptor (TCR) affinity, genetic engineering, and structural immunobiology, the Klebanoff laboratory seeks to address both factors currently limiting the application of ACT for advanced solid cancers.