T cells expressing a chimeric‐PD1‐Dap10‐CD3zeta receptor reduce tumor burden in multiple murine syngeneic models of solid cancer

Adoptive transfer of T cells is a promising therapy for many cancers. To enhance tumor recognition by T cells, chimeric antigen receptors (CAR) consisting of signaling domains fused to receptors that recognize tumor-associated antigens can be expressed in T cells. While CAR T cells have shown clinical success for treating hematopoietic malignancies, using CAR T cells to treat solid tumors remains a challenge. We developed a chimeric PD1 (chPD1) receptor that recognizes the ligands for the PD1 receptor which are expressed on many types of solid cancer. To determine if this novel CAR could target a wide variety of tumor types, the anti-tumor efficacy of chPD1 T cells against syngeneic murine models of melanoma, renal, pancreatic, liver, colon, breast, prostate, and bladder cancer was measured. Of the fourteen cell lines tested, all expressed PD1 ligands on their cell surface, making them potential targets for chPD1 T cells. ChPD1 T cells lysed the tumor cells and secreted pro-inflammatory cytokines (IFNgamma, TNFalpha, IL-2, GM-CSF, IL-17, and IL-21) but did not secrete the anti-inflammatory cytokine IL-10. Furthermore, T cells expressing chPD1 receptors reduced an established tumor burden and led to long-term tumor free survival in all types of solid tumors tested. ChPD1 T cells did not survive longer than 14 days in vivo, however treatment with chPD1 T cells induced protective host anti-tumor memory responses in tumor-bearing mice. Therefore, adoptive transfer of chPD1 T cells could be a novel therapeutic strategy to treat multiple types of solid cancer.