Augmentation of Antitumor Immunity by Human and Mouse CAR T Cells Secreting IL 18
SUMMARY The effects of transgenically encoded human and mouse IL 18 on T cell proliferation and its application in boosting chimeric antigen receptor (CAR) T cells are presented. Robust enhancement of proliferation of IL 18 secreting human T cells occurred in a xenograft model, and this was dependent on TCR and IL 18R signaling. IL 18 augmented IFN g secretion and proliferation of T cells activated by the endogenous TCR. TCR deficient, human IL 18 expressing CD19 CAR T cells exhibited enhanced proliferation and antitumor activity in the xenograft model. Antigen propelled activation of cytokine helper ensemble (APACHE) CAR T cells displayed inducible expression of IL 18 and enhanced antitumor immunity. In an intact mouse tumor model, CD19 IL 18 CAR T cells induced deeper B cell aplasia, significantly enhanced CAR T cell proliferation, and effectively augmented antitumor effects in mice with B16F10 melanoma. These findings point to a strategy to develop universal CAR T cells for patients with solid tumors.
Cell reports