Figure 1.

M11 CAR T Cells Exert Minimal Bystander Effects in a Syngeneic Malignant Mesothelioma (MM) Mouse Model

A mouse model of MM was developed, using murine AE17 MM cells, transduced with chicken ovalbumin and human mesothelin (AE17om). 2 million AE17om cells were injected into the right flanks of B6 mice, which, by day 3 post-injection, developed into established tumors ∼50 mm³ in size. (A) The schema used to cure these tumors involved two doses of 10⁷ transduced M11 CAR T cells each, given intravenously on day 4 and day 6 post-tumor inoculation. All experiments were repeated at least twice; n = 8 mice per group. (B) Tumor growth measurements over time show tumor cure. (C) M11 CAR T cells did not have an effect on tumors negative for mesothelin. AE17om cells were mixed with varying percentages of AE17o cells, i.e., cells that expressed ovalbumin but not human mesothelin, to assess whether our treatment schema could eradicate tumors that did not universally express the target antigen. (D) M11 CAR T cells could not cure tumors that were 50% mesothelin positive. (E) M11 CAR T cells could not cure tumors that were 75% mesothelin positive. (F) M11 CAR T cells could not cure tumors that were 90% mesothelin positive.