Abstract Title: Glioblastoma Multiforme Tumor Volume and Persistence of Chimeric Antigen Receptor T Cells Following Treatment

Background: Glioblastoma Multiforme (GBM) is one of the most common and aggressive high-grade primary brain tumors that arises from the glial cells of the central nervous system and occurs most often in the frontal and temporal lobes. Despite current treatment options, long-term prognosis of GBM remains low with no significant improvement rates. Chimeric antigen receptor (CAR)-expressing T cells target the B cell marker CD19 and have shown increased efficacy in B cell lymphomas, acute lymphoblastic leukemia, and chronic lymphocytic leukemia suggesting benefits in GBM. B7-Homologue3 (B7-H3) is a type 1 transmembrane glycoprotein that shares homologous domains with PD-L1 and recently gained increased attention as an important immune checkpoint molecule. B7-H3 is highly expressed in GBM, contributing to tumor invasiveness, metastatic potential, and poor outcomes, making it an ideal target for immune therapies. This study aims to quantify the persistence of CAR-T cells in the context of GBM tumor volume following neurosurgical debulking procedure.

Methods: For imaging, a radiology software known as the mint Lesion was utilized to provide Tumor Response Assessment by Criteria (TRAC) reports that consist of volumetric measurements of the tumor lesions (target enhancing lesions, non-target enhancing lesions, and non-target non-enhancing lesions). The Response Assessment in Neuro-Oncology (RANO) criteria is used as a radiologic assessment of treatment response in high-grade gliomas. Fluorescence-activated cell sorting (FACS) is a type of flow cytometry technique that uses highly specific antibodies labeled with fluorescence conjugates. FACS analysis takes a sample mixture of cells and sorts them into different populations based on their specific biomarkers and fluorescence characteristics and with the help of Cytek Aurora, separates the cells into various groups to provide a graphical representation.

Results: B7-H3 CAR-T cell persistence was increased in patients with a larger post-surgical tumor volume. CAR-T cells remained detectable till the end of the cycle (Day 28) for all subjects. This was reflected through the ratio of the percentage of CD8 CAR-T cells and the follow-up tumor volume. Increased B7-H3 CAR-T cell persistence was demonstrated with a larger ratio and reflected a larger post-surgical tumor volume.

Conclusion: To conclude, B7-H3 CAR-T cells are highly persistent in patients with a large post-surgical tumor volume making CAR-T cell therapy a more promising regimen in patients with the first recurrence of glioblastoma.