Poster #017, Stanford University
Tracking B7-H3 CAR T-Cell Dynamics in Recurrent Glioblastoma
Mentors: Bita Sahaf, PhD, Reena Thomas, MD, PhD and David Miklos, MD, PhD
Glioblastoma (GBM) is the most common malignant primary brain tumor in adults, with approximately 13,000 new cases diagnosed annually in the United States and a median survival of 14-18 months. Current treatment options for recurrent GBM remain limited, creating an urgent need to develop and mechanistically characterize new cellular therapies.
One emerging and promising therapy harnesses B7-H3-targeting chimeric antigen receptor (CAR) T cells, currently being evaluated in a Phase I clinical trial. The CART expansion, persistence, and immune effects across blood and the central nervous system are being studied. This project aimed to characterize longitudinal B7-H3 CAR T-cell dynamics and explore how these patterns relate to immune phenotype changes and treatment response.
We analyzed longitudinal patient samples collected before and after repeated B7-H3 CAR T-cell infusions. Clinical course was summarized using a swimmer plot. Leveraging a CAR specific flow cytometry assay (CAR-FACS), we quantified total, CD4+, and CD8+ CAR T-cell frequencies in peripheral blood mononuclear cells (PBMC) and cerebrospinal fluid (CSF), while qPCR measured B7-H3 CAR DNA as a complementary marker of CAR T-cell persistence. Single-cell RNA sequencing and regulatory T-cell analyses were used to examine immune phenotype changes following infusion.
Clinical courses varied across patients, with differences in treatment duration, progression, follow-up, and response patterns. CAR-FACS revealed patient and compartment-specific CAR T-cell expansion, with higher CAR+ T-cell frequencies observed in CSF compared to PBMC. qPCR indicated patient-specific B7-H3 CAR DNA dynamics in PBMCs, including transient peaks following infusion. Single-cell and regulatory T-cell analyses suggested shifts in immune-cell composition over time, including changes in regulatory T-cell populations that may relate to CAR T-cell persistence.
These findings highlight patient and compartment-specific immune dynamics following B7-H3 CAR T-cell therapy and support further investigations into how CAR T-cell expansion, persistence, and regulatory or myeloid immune changes relate to treatment response.