Objective:

This study aims to quantify the persistence of CAR-T cells in the context of GBM tumor volume following neurosurgical debulking procedure.

Background:

Glioblastoma Multiforme is a common and aggressive high-grade primary brain tumors that arises from glial cells of the CNS and occurs in the frontal and temporal lobes. Despite current treatment options, long-term prognosis of GBM remains low with no significant improvement. Chimeric antigen receptor expressing T cells target the B cell marker CD19 and have shown increased efficacy in lymphomas and leukemias, suggesting benefits in GBM. B7-Homologue3 is a type 1 transmembrane glycoprotein that gained increased attention as an important immune checkpoint molecule and is highly expressed in GBM, contributing to tumor invasiveness, metastatic potential, and poor outcomes, making it an ideal target for immune therapies.

Design/Methods:

The radiology software mint Lesion was utilized to provide Tumor Response Assessment by Criteria reports that consist of volumetric measurements of the tumor lesions (target enhancing lesions, non-target enhancing lesions, and non-target non-enhancing lesions). Fluorescence-activated cell sorting is a type of flow cytometry technique that takes a sample mixture of cells and sorts them into different populations based on their specific biomarkers and fluorescence characteristics and 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.

Conclusions:

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.