SAHA Enhances CAR T Cell Cytotoxicity and Increases B7-H3 Surface Expression in Human Neuroblastoma

Overview

Neuroblastoma is a pediatric cancer arising from mutated embryonic nerve cell precursors. It is the most common extracranial pediatric solid tumor, yet current therapies are associated with significant toxicity and relapse. Chimeric antigen receptor (CAR) T-cell therapy involves genetically modifying patients’ own T lymphocytes to (1) recognize tumor cells by antigens found on their surfaces, and (2), kill the tumor cells. CAR T-cells have been effective at targeting liquid cancers, such as leukemias, but face several obstacles with solid tumors. The compound suberoylanilide hydroxamic acid (SAHA) has been shown to upregulate B7-H3, a tumor-associated antigen, on the surface of solid tumor cells, including breast, lung, and melanoma. This study investigated whether SAHA treatment would upregulate B7-H3 surface expression on neuroblastoma cells and enhance the efficacy of CAR T cells expressing B7-H3 receptors. Human neuroblastoma cell lines CHLA-255 and LA-N-5 were treated with 0, 0.25, 0.5, and 1 µM SAHA for 48, 120, and 168 hours. B7-H3 surface expression was then quantified by flow cytometry. The result was a statistically significant time- and SAHA dose-dependent increase in surface expression of B7-H3. CHLA-255 cells were treated with SAHA for 168 hours to upregulate B7-H3 surface expression, and then treated with B7-H3 CAR T cells. Cells pretreated with SAHA experienced greater CAR T cell cytotoxicity across multiple conditions. These findings demonstrate that SAHA effectively upregulates B7-H3 surface expression and improves CAR T cell cytotoxicity in human neuroblastoma cells.

Competition history

• CSEF 2026 Medicine & Physiology (Senior Division) · Entry S-15-36

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