LAUSR

12Background: Immune escape via downregulation of tumor associated antigens (TAAs) is an important mechanism of resistance to Chimeric Antigen Receptor (CAR) T cell therapy. Particularly in solid tumor malignancies where antigen expression could be heterogeneous, the risk of antigen-low or antigen-negative relapse is significantly high. One strategy to overcome this limitation is to reengineer CAR T cells to engage other arms of the immune system such as endogenous cytotoxic T cells and dendritic cells (DC) to broaden the antitumor response beyond the TAA targeted by CAR T cells. This could be achieved by co-modifying CAR T cells with Interleukin-12 (IL-12). IL-12 is a proinflammatory cytokine produced by DCs, and macrophages, and has been shown to promote maturation of DCs and increase T-cell proliferation. We hypothesized that CAR T cells genetically engineered to constitutively secrete IL-12 will be efficacious against Muc16ecto low (MLo) and Muc16ecto high (MHi) heterogeneous tumors in a syngeneic mou...