EXTH-53. IL-12 ARMORED CAR T CELL THERAPY FOR HETEROGENEOUS GLIOBLASTOMA

Abstract INTRODUCTION Chimeric antigen receptor (CAR) T cells specific for the glioblastoma (GBM)-specific epidermal growth factor variant III (EGFRvIII; CARvIII) have successfully treated tumors homogeneously expressing EGFRvIII when combined with lymphodepletion, however this is not recapitulated clinically. We generated an “armored” CARvIII which constitutively secretes IL-12, a stimulatory cytokine that enhances cell persistence and function, capable of treating orthotopic heterogeneous GBM in immune competent mice. METHODS C57Bl/6 mice were intracranially (IC) implanted 5 x 105 either homogenous (CT2AvIII) or (1:1 CT2AvIII CT2A parental) tumor cells. Mice 2 106 IL-12 seven days post implant monitored survival. TCRα -/-, CD8-/- IC homogeneous 7 intracranial therapy to assess role endogenous within microenvironment characterized by flow cytometry 8, 14, 17 implantation. RESULTS generated, secreted cytotoxic against EGFRvIII-expressing vitro. was curative (p< 0.0001) conferred long-term survival 50% CT2AvIII:CT2A parental vivo 0.0001). Furthermore, eradicated -/- but failed produce any efficacy (p=0.0002). Endogenous found be more migratory, interestingly exhausted than CONCLUSIONS Our findings show can effectively eradicate without lymphodepletion. Surprisingly, IL12 also glioma. Heterogeneous clearance required CD8 response.