Abstract

Cancer immunotherapy is a way of treating cancers by harnessing the patient’s own immune system to kill cancer cells. One type of cancer immunotherapy called chimeric antigen receptor (CAR) T-cell therapy involves taking patients’ T-cells, retargeting them to molecules on cancer cells, stimulating cell division to generate large numbers and putting them back into the patient. For leukemias and lymphomas, CAR -T therapy targeting a molecule called CD19 represents the most promising breakthrough in the past decade with 40 – 50% of lymphoma patients with a poor prognosis having a complete and long-lasting response. However, the response rate of CD19 -CAR-T therapy in other blood cancers with a poor prognosis can be as low as 25%. In solid cancers such as pancreatic cancer, CAR -T response rates are as low as 17%.

Our work studying how T cells detect and infiltrate cancers using preclinical models has shown that L-selectin expression by cancer specific T-cells is essential to restrict the growth of solid and disseminated cancers. These studies have revealed a strategy for increasing the efficacy of T cells by enhancing expression of L-selectin. We are currently testing whether L-selectin can be used to modify CAR -T cells to broaden their use in the clinic.