IMMU-17. DEVELOPMENT OF AN INTRACRANIAL CANNULA IMPLANTATION SYSTEM FOR SERIAL LOCOREGIONAL CAR T CELL INFUSIONS IN MICE

Abstract

Abstract Pediatric CNS tumors are responsible for the majority of cancer-related deaths in children. As many tumors lack efficacious treatments, there is a crucial need to develop more promising therapeutic options, such as immunotherapies. Of particular interest is the use of chimeric antigen receptor (CAR) T cell therapy. Current clinical trials are ongoing targeting the cell surface molecules HER2, EGFR, B7-H3, IL13RA2, and the disialoganglioside GD2. While the majority of trials deliver CAR T cells into the cerebral spinal fluid with repeated doses, this has not been completed in preclinical models due to difficulty performing multiple stereotactic surgeries. To evaluate repeated locoregional delivery of CAR T cells in preclinical murine models, we established an indwelling catheter system that recapitulates indwelling catheters currently being used in human clinical trials. Following orthotopic injection and engraftment of tumor cells in mice, intratumoral placement of a fixed guide cannula is completed on a stereotactic apparatus and secured with screws and acrylic resin. Treatment cannulas are then inserted through the fixed guide cannula for repeated CAR T cell delivery. With this system, we tested novel CAR T cells directed against glypican 2 (GPC2), resulting in significant tumor regression in medulloblastoma model 7316-4509 (p<0.01), as well as significantly prolonged survival in thalamic diffuse midline glioma 7316-3058 (p<0.05). Stereotactic placement of the guide cannula can be adjusted to deliver CAR T cells directly into the lateral ventricle or other locations in the brain. This platform offers a reliable mechanism for preclinical testing of repeated intracranial infusions of CAR T cells and other novel therapeutics, offering a superior preclinical model for translation to clinical trials.