EXTH-45. TARGETING GLIOBLASTOMA BY NOVEL INTEGRIN-SPECIFIC CAR T CELLS

Abstract RATIONALE Innovative treatment strategies are urgently needed to improve the prognosis of glioblastoma patients. Chimeric antigen receptor (CAR) T cell therapy has shown great success in hematological malignancies. However, it remains be that CAR cells also active against solid tumors. αv integrins overexpressed gliomas and have already been used as therapeutic targets for small molecule inhibitors antibodies. While these approaches were well tolerated, they did not exert meaningful clinical activity We aimed at exploiting presence anti-glioma therapy. METHODS targeting specific integrin heterodimers (αvβ3, αvβ5 or αvβ8) generated their was determined co-culture assays with different glioma cells. The efficacy control tumor growth vivo assessed clinically relevant orthotopic mouse models. RESULTS All newly integrin-targeting exerted strong anti-tumor vitro. highest lytic observed αvβ8 integrin-specific from patient-derived immune displayed when tested autologous tumors Glioma a CRISPR/Cas9-mediated knockout target resistant cell-mediated cytotoxicity demonstrating specificity. 2 Intratumoral glioma-bearing mice significantly prolonged survival cured substantial fraction animals. CONCLUSION αvβ5- αvβ8-specific target-specific vitro prolong mice. These data form basis evaluation glioblastoma.