Abstract 618: Toll-like receptor 2 costimulation potentiates the antitumor efficacy of CAR T cells

Chimeric antigen receptor(CAR) T cell immunotherapies have shown unprecedented success in treating leukemia but lack efficacy in solid tumors. Here, we generated 1928zT2 and m28zT2, targeting CD19and mesothelin, respectively, by introducing the Toll/ interleukin-1 receptor(TIR) domain of Toll-like receptor2 ( TLR2) to 1928z and m28z. T cells expressing 1928zT2 or m28zT2 showed enhanced effector function, expansion and persistency against CD19+ leukemic or mesothelin+ lung cancer cells in vitro and in vivo. In a patient with relapsed B cell acute lymphoblastic leukemia, a single dose of 5×104/kg 1928zT2 T cells resulted in robust expansion and leukemia eradication and led to complete remission. Hence, our results demonstrate that TLR2signaling is a contributing component to CAR T cells for both leukemia and solid tumors and is capable of increasing the efficacy of CAR T cells and facilitating low dose clinical usage. Citation Format: Peng Li, Xin Du, Yun Xin, Jianyu Weng, Peilong Lai. Toll-like receptor2 costimulation potentiates the antitumor efficacy of CAR T cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 618. doi:10.1158/1538-7445.AM2017-618