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 limited clinical efficacy in solid tumors. Here, we generated 1928zT2 and m28zT2, targeting CD19 and mesothelin, respectively, by introducing the Toll/interleukin-1 receptor (TIR) domain of Toll-like receptor 2 (TLR2) to 1928z and m28z. T cells expressing 1928zT2 or m28zT2 showed improved expansion, persistency and effector function against CD19⁺ leukemia or mesothelin⁺ solid tumors respectively in vitro and in vivo. In three patients with relapsed B cell acute lymphoblastic leukemia, a 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 TLR2 signaling can contribute to the efficacy of CAR T cells. We will present updates on the clinical trial.