Exploring Armored CAR T-cell Therapies for Hepatocellular Carcinoma

 A new, first-in-humans clinical trial for hepatocellular carcinoma uses an “armored” CAR T-cell therapy designed to resist the hostile tumor microenvironment found in 77% of patients with this disease.

Marco Davila, MD, PhD, Senior Vice President and Associate Director for Translational Research, and Anuradha Krishnamurthy, MBBS, an Associate Director of Early Phase Clinical Trials for Solid Tumor Cell Therapies, both at Roswell Park Comprehensive Cancer Center, explain the new trial, which will target the antigen GPC3, a protein that has been investigated in other clinical trials. “We wanted to armor these cars with the ability to resist the hostile hepatoma tumor microenvironment,” editing out a gene for a “highly immune suppressive cytokine,” Dr. Davila says. “The hope is that when we edit this receptor out, and put (the new cells) into patients, it will be able to not be suppressed by this cytokine,” allowing the treatment to be more successful.

Roswell Park is actively recruiting new patients for this trial. A patient is eligible if they have advanced unresectable or metastatic hepatocellular carcinoma, have previously progressed or been intolerant to checkpoint inhibitors or tyrosine kinase inhibitors, Dr. Krishnamurthy says.