IMMU-22. ALLOGENEIC NK CELLS SECRETING IL15 AND RESISTANT TO TGF-β Show Antitumor Activity Against Gliobastoma

Abstract INTRODUCTION High grade brain cancers, like most solid tumors, often relapse and are resistant to current therapies. Limited efficacy cell therapy may be related intratumoral heterogeneity the suppressive tumor microenvironment. Hence, we aimed modify allogeneic natural killer (NK) cells, which can recognize expressed stress ligands, resist TGF-β secrete IL15. METHODS Cord blood-derived NK cells were expanded modified express IL15 a dominant negative receptor (DNR) against TGF-β. product activity GBM line U87MG evaluated in vitro vivo. The behavior of these also analyzed ex vivo, evaluate impact (including potential toxicity) increasing potency this product. RESULTS While animals injected with secreting expressing DNR successfully cleared tumors 6 days after T infusion, did not observe significant differences survival between groups (no treatment control mice vs treated mock-transduced DNR-transduced IL-15/DNR-transduced cells). Therefore, sought determine whether cytokine-related toxicity was responsible for death setting clearance. We compared no or products. Elevated levels IL-15 detected plasma cells. These elevated corresponded persistence measured by ddPCR. However, other cytokines upregulated. CONCLUSIONS observed improved clearance when both protected immune capable stimulatory cytokine currently performing additional experiments from secretion occurs. To potentially mitigate plan engineer suicide gene into constructs.