EPEN-04. DEVELOPMENT OF B7-H3-TARGETED CAR T CELL THERAPY FOR EPENDYMOMA

• DOI: 10.1093/neuonc/noad073.108
• Publication Date: 2023-06-12T19:42:53Z
• Authors: Sanya Mehta; Haley Houke; Jorge Ibanez; Erik Emanus; Stephen Mack; Giedre Krenciute
• Keywords: 03 medical and health sciences; 0302 clinical medicine; Final Category: Ependymoma - EPEN

Abstract Targeted treatment options are desperately needed for ependymomas (EPN). Chimeric antigen receptor (CAR) T cells have immense potential to positively transform outcomes; however, little is known regarding antitumor efficacy of CAR against EPNs. We found that B7-H3 highly expressed on pediatric brain tumor patient-derived orthotopic xenografts from EPN patients, making it a promising target CAR-T cells. The project’s goal develop safe, effective targeted cell immunotherapy EPN. generated second generation human B7-H3-CAR and examined their anti-EPN cytolytic activity, expansion, cytokine production. had potent in vitro activity all lines tested (1425, ST1, CPITT, ST2, EPI, L6SJ). In repeated-stimulation assays, expanded 7-10 times, up one million-fold when co-cultured with Interestingly, while the were secrete high levels C-C motif chemokine ligand 2 (CCL2) which consistent published data, our Multiplex analysis co-culture supernatants shows CCL2 production increased 10-fold Finally, we demonstrate supratentorial-EPN xenograft mouse model (1425 line) without apparent toxicities, although 4 out 12 tumors re-lapsed. Recurrent underway. Together, data establishment clinically relevant study resistance therapy EPN, preliminary mechanistic insight into persistence modulation through signaling. Given about function its receptor, type (CCR2) EPNs or cells, future work will focus defining these biological mechanisms, enabling us improvements