Developing New And Effective Strategies For Adoptive T- Cell Therapy In Pediatric Gliomas

Tumors of the central nervous system are the most common form of childhood malignancy and differ from their adult counterparts. Cancer immunotherapy holds a lot of potential as a targeted therapy designed with high affinity to locate specifically the tumor cells and act directly on them, however, its applicability in the context of gliomas seems limited, in part, by the lack of ubiquitously expressed tumor antigens. We have developed elegant immunocompetent mouse models of pediatric brain tumors by cloning mutations/fusions found in human pediatric patients into Cre/loxP-inducible lentiviral vectors. The lentiviruses are intracranially injected to Cre transgenic postnatal pups. In this study, we focused on FGFR1 mutations and characterized the tumors obtained by lentiviral injection into postnatal mice. On the CAR-T side, we identified a novel tumor associated antigen that is expressed at the cell surface of tumor cells and it is not expressed on the surface of healthy/normal tissue. Murine specific CAR-T engineered lymphocytes were tested in vitro against pediatric glioma cell lines, resulting in activation of the engineered T cells and a significant cytotoxic effect. Next we plan to assess the efficacy of the engineered CAR T cells in vivo using our pediatric brain tumor model. In addition we will track the CAR-T cell migration and infiltration (biodistribution) using GNP (gold nanoparticles) that can be tracked using CT screening. Our studies identified a previously uncharacterized biomarker, which is highly expressed in pediatric gliomas that holds potential for serving as a novel CAR-T target for cancer immunotherapy in pediatric gliomas.