A novel CAR T-cell therapy available only at Roswell Park Comprehensive Cancer Center is leveraging genome-editing technology to target the glypican-3 (GPC3) protein, which is often expressed in hepatocellular carcinoma (hepatoma) liver cancers — but rarely in healthy tissue.

Patients are now being enrolled on a phase 1 clinical trial of RPCAR01 (NCT06968195) to evaluate the safety and toxicity of this approach in patients with GPC3-expressing advanced or metastatic hepatocellular carcinoma. Anuradha Krishnamurthy, MBBS, Associate Director of Early Phase Clinical Trials for Solid Tumor Cell Therapies at Roswell Park, is Principal Investigator of the study.

Typically, patients with advanced/metastatic hepatomas survive only a few months to a year. While patients with hematological malignancies have benefited significantly from CAR T-cell therapies — seven of which are now FDA-approved — the tumor microenvironment has presented challenges in the treatment of solid tumors. This clinical trial advances Roswell Park’s goal of developing innovative CAR T-cell therapies to extend those benefits to patients with solid tumors.

Patients’ own T lymphocytes will be collected and engineered to target GPC3 and prevent the cell-signaling protein known as transforming growth factor beta (TGF?) from suppressing the T cells’ cancer-killing potential. The cells will be processed in Roswell Park’s GMP Engineering & Cell Manufacturing Facility, the largest academic facility of its kind in the nation and New York State’s first “hub” supporting cellular therapy. The anti-GPC3 CAR T cells will then be expanded and returned to the patient.

Investigators expect to enroll 24 participants, with first patients to be treated on the study in fall/winter 2025. The clinical trial is sponsored by Roswell Park.