EXTH-138. GD2 as an Immunotherapeutic Target in Oligodendroglioma: Preclinical Evidence Supporting CAR T Cell Therapy

BACKGROUND Oligodendrogliomas are a distinct subtype of diffuse gliomas that arise from glial cells resembling oligodendrocytes. While associated with a relatively favorable prognosis compared to other diffuse gliomas, oligodendrogliomas are inherently infiltrative and ultimately progressive. Immunotherapy using GD2-targeted chimeric antigen receptor (CAR) T cells has shown early promise in H3K27M-mutant diffuse midline gliomas (DMGs), which consistently express high levels of GD2. Given that both oligodendrogliomas and DMGs can originate from oligodendroglial lineage cells, we hypothesized that GD2 could serve as a viable immunotherapeutic target in oligodendroglioma. METHODS We performed immunohistochemistry staining on 34 frozen oligodendroglioma tissue samples, including newly diagnosed and recurrent cases. GD2 expression was quantified and compared to DMG tissue, which served as a positive control. To evaluate in vitro cytotoxicity, we used a patient-derived oligodendroglioma cell line previously validated to express high GD2 levels. GD2-CAR T cell–mediated tumor killing was assessed over 72 hours at increasing effector-to-target (E:T) ratios and cytokine production was measured after 24 hours of co-culture. Statistical analysis was performed using t-tests and one-way ANOVA with pairwise comparisons (p < 0.05). RESULTS The immunohistochemistry analysis revealed that 29/34 oligodendroglioma samples expressed GD2: 8/34 samples exhibited high GD2 expression at levels comparable to DMG, 21/34 samples expressed GD2 at moderate though variable levels, and 5/34 samples exhibited limited GD2 expression. In vitro, GD2-CAR T cells induced robust, dose-dependent cytotoxicity against patient-derived oligodendroglioma cells, significantly exceeding mock and CD19-CAR T cell controls. This cell killing was accompanied by elevated levels of IFN-γ, IL-2, TNF-α, CXCL10, and IL-6, indicating antigen-specific immune activation. CONCLUSIONS These preclinical findings demonstrate that GD2-CAR T cells elicit potent cytotoxic and immunostimulatory responses against oligodendroglioma, supporting the rationale for developing a clinical trial protocol evaluating GD2-CAR T cell therapy in recurrent oligodendroglioma patients, for whom there are limited treatment options.