114P Engineering logic-gated cytokine circuits in CAR T cells targeting sarcoma

Sarcomas are mesenchymal solid tumors with limited treatment options in advanced disease. Combinations of tyrosine kinase inhibitors with immune checkpoint blockade show ∼30–40% 6-month progression-free survival, indicating potential for immunotherapy in sarcoma including CAR T cells. However, standard CAR T cells perform poorly against most solid cancers due to physical barriers and immunosuppressive tumor microenvironments (TME) that impair persistence and effector activity. To address these challenges, we developed a next-generation CAR T cell strategy to convert suppressive signaling into stimulation, and to harness endogenous antitumor immunity.