EXTH-84. A NOVEL DUAL-SPECIFIC CHIMERIC ANTIGEN RECEPTOR T CELL WITH HIGH SPECIFICITY FOR EGFR AND EGFRVIII IMPROVES SURVIVAL IN EGFR EXPRESSING MEDULLOBLASTOMA

Abstract BACKGROUND Medulloblastoma is the most common malignant brain tumor in children 0-19 years of age and current treatment requires surgical resection, followed by high dose chemotherapy radiotherapy. Therapy carries morbidity, with late effects including neurocognitive decline, endocrine dysfunction, subsequent malignancies. Chimeric antigen receptor (CAR) T cell therapy presents potential for less toxic more effective medulloblastoma. Epidermal growth factor (EGFR) expressed medulloblastoma derived lines appears to serve an important role metastatic this type. D2C7 a recombinant monoclonal antibody short chain variable fragment (scFv) dual specificity, binding wild type EGFR (EGFRwt) its mutant variant III (EGFRvIII). We previously developed novel, third-generation chimeric T-cell construct utilizing scFv performed analysis on both glioblastoma models. METHODS U87 U87vIII DAOY were characterized flow cytometry evaluate EGFRwt EGFRvIII expression. Cytotoxicity assays serially diluted effector: target ratios U87, U87vII, mixed CAR. was orthotopically implanted into frontal lobe NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ (NSG) mice. After implantation, CAR introduced within bed. RESULTS detected U87vIII, analysis. only U87vIII. demonstrated vitro cytotoxicity against all three >90% achieved at ratio 2.5:1. In vivo, significantly prolonged survival compared mock CONCLUSION demonstrates efficacy mouse models glioblastoma. Future steps our work will set out assess NSG mice posterior fossa.