Poster #064, Stanford University
Immune Cell Dynamics in a Phase I Trial of B7-H3 CAR T-cells for Glioblastoma
Mentors: Bita Sahaf, PhD, David Miklos, MD, PhD and Reena Thomas, MD, PhD
Recurrent Glioblastoma Multiforme (GBM) accounts for approximately half of all malignant brain tumors, and has a low five-year survival rate at around 5%, with tumor-initiating stem cell populations believed to contribute to recurrence and therapeutic resistance.
In various tumor types, including GBM, the transmembrane protein B7-H3 (CD276) is typically overexpressed, compared to healthy brain tissue. B7-H3 Chimeric Antigen Receptor T-cell (CAR T-cell) therapy involves genetically modifying a patient’s own T cells to specifically target B7-H3 for tumor cell clearance. Here, we evaluated CAR T-cell expansion, B7-H3 expression, and immune cell dynamics in a phase I trial of B7-H3 CAR T-cell treatment in GBM. Twelve patients with high-grade GBM received B7-H3 CAR T-cell therapy after tumor resection. We then performed flow cytometry to quantify CAR T-cells and single-cell RNA sequencing (scRNA-seq) to analyze the genes expressed in cerebrospinal fluid (CSF) and peripheral blood mononuclear cell (PBMC) samples. Through scRNA-seq we confirmed that all patient’s tumor cells expressed B7-H3 before CAR T-cell treatment. Additionally, our results revealed CD4+ and CD8+ CAR T- cell expansion in the first two cycles, followed by less expansion in the following treatment cycles. Finally, macrophage cell presence peaked in the first three days post-CAR-T infusion in CSF before decreasing in the CSF, which coincided with increased B7-H3 CAR T-cells in the CSF.
These findings suggest that B7-H3 CAR T-cell therapy induces robust CAR T-cell expansion in early cycles and may reduce immunosuppressive macrophages as well as promote CD8+ T-cell growth. Our results support further investigation of B7-H3 CAR T-cell therapy as a treatment for GBM, which shows promising therapeutic potential.