Figure 2.

M11 CAR T Cells Combined with Immunomodulatory Therapies Are Unable to Induce Bystander Effects in 90% Mesothelin-Positive Tumors

We used the treatment schedule that cured the 100% mesothelin-positive AE17om tumors with the addition of several immunomodulatory therapies in order to augment the ability of M11 CAR T cells to cure 90% mesothelin-positive AE17om tumors. All experiments were repeated at least twice; n = 8 mice per group. (A) The use of anti-PD-1 antibody (5mg/kg, given i.p. two times per week) resulted in some tumor regressions both as a single agent and in combination with M11 CAR T cells; however, no cures were observed. (B) Anti-CTLA-4 antibody (200 μg per mouse, given i.p. two times per week) did not have an effect as a single agent and only minimally increased cytotoxicity of M11 CAR T cells when given in combination. (C) Administration of an anti-TGF-β antibody (150 μg per mouse, given i.p. two times per week) had a synergistic effect with M11 CAR T cells and stopped tumor growth; however, only temporarily. (D) Agonistic CD40 antibody (40 μg per mouse, given i.p. as a single dose on day 7; 1 day after the 2nd dose of M11 CAR T cells) had no effect, either as a single agent or in combination with M11 CAR T cells. (E) The use of an IDO inhibitor (300 mg/kg, given by oral gavage daily for 2 weeks, starting on day 3 after tumor inoculation) did not enhance efficiency of M11 CAR T cells.