Figure 3.

CAR-T cell therapy combined with radiotherapy in mice bearing subcutaneous CAPAN-2 tumors. (A) In the efficacy studies using the CAPAN-2 tumor model the radiation was given in one fraction on day 10 (4Gy) post-tumor implantation when tumors reached ~7mm in diameter and the infusion was administered on day 11 (dark green); if the radiation included four doses (1Gy x 4 fractions) on days 10, 11, 12, and 13; the mice received the infusion 24h after the last fraction on day 14 (light green). In a single experiment, we determined the efficacy of multiple radiation doses combined with a single dose of CAR-T cell therapy. In all four radiation dose groups in this experiment (B–E), mice treated with dual therapy showed superior tumor control compared with mice receiving monotherapies. Mice treated with 1Gy x 4 fractions plus CAR-T cell therapy showed marginally better control of tumor growth relative to radiation or CAR-T cells alone (B). Notably, the use of 4Gy x 1 fraction combined with CAR-T cell therapy resulted in the most significant tumor control (C) and a 100% survival rate (F1) at day 75 [i.e., compared to mice receiving CAR-T cells (p<0.005) or 4Gy x 1 fraction of LDRT (p<0.0003)]. Also, relative to LDRT alone (p<0.0001) and CAR-T therapy alone (p<0.0001), 2 Gy x 2 fractions combined with anti-mesothelin CAR-T cells also significantly improved tumor control (D) and survival (F2). In addition, 2 Gy x 1 fraction + CAR-T cells (E) was marginally, but not significantly better than 1Gy x 4 fractions + CAR-T cells. (n=5 mice per group).