Super2-IL-33 armored CAR T cells reshape the tumor microenvironment to universally suppress solid tumor growth

Abstract Tumor associated immunosuppressive cells limit the efficacy of CAR T against solid tumors. To alter immunosuppression in tumor microenvironment, were armored with an IL-2 superkine (Super2) and alarmin IL-33 adoptively transferred into immunocompetent mice established primary or metastatic B16F10 melanoma intradermal MC38 colon carcinoma. We show that Super2-IL-33 universally promoted control tumors mice. Analysis infiltrating lymphocytes (TILs) revealed Super2 expanded endogenous cells, resulting increased ratio CD8 effector to regulatory cells. The expression molecules was dispensable for cell-induced control, underscoring contribution immune mediating therapeutic efficacy. next evaluated effects bone, liver, thymus (BLT) humanized assess human model. BLT intradermally inoculated Caki1, a renal cell carcinoma which non-treated are highly enriched determine impact on growth TILs analyzed. recruit facilitate suppression growth. Thus, cytokine combination may serve as universal platform capable overcoming promote broad anti-tumor immunity. Supported by grants from NIH (R43-CA271880 R01-CA254042)