Adoptive T-cell Immunotherapy With Potential Dual Function For The Treatment Of Glioblastoma

Glioblastoma (GBM) is the most common and lethal form of brain cancer. 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 GBM context it seems limited, in part, by the lack of ubiquitously expressed tumor antigens.

Previously, we identified P32/gC1qR/HABP, a mitochondrial protein that is expressed at the cell surface of tumor cells and tumor derived endothelial cells (TDECs), as a glioma cell surface-marker that could be targeted by immunotherapy. Human and murine glioma cells were evaluated for expression of p32 by flow cytometry and confocal microscopy. Human and murine p32-specific CAR engineered lymphocytes were tested in vitro against human and murine glioma lines. The antitumor efficacy of this CAR was evaluated in a syngeneic mouse GBM model and in human xenograft model, showing in both models a significant survival extension in the treated groups. Antiangiogenic activity of the CARs was evaluated in vitro against tumor derived endothelial cells (TDEC), resulting in activation of the engineered T cells and a significant cytotoxic effect. Confocal microscopy analysis of tumor sections, showed reduced blood vessels (vWF staining) in the p32-CART treated group, supporting the potential antioangiogenic effect of these CARs.
Collectively, our studies identified a previously uncharacterized biomarker, p32, expressed both in glioma cells and TDECs that holds potential for serving as a novel CAR target with a dual function for cancer immunotherapy in gliomas.