Overview

• CRISPR/Cas9-mediated knockout of the IFN-γ receptor in CAR-T cells reduces activation-induced cell death and prolongs cell persistence in vitro and murine tumor models.
• Modified CAR-T cells maintain interferon-γ release for tumor killing and resist IFN-γ-induced feedback that triggers cell death.
• Preclinical studies showed that IFN-γ receptor-deficient CAR-T cells achieved greater expansion and anti-tumor activity in multiple solid tumor models.
• Researchers plan a phase 1 clinical trial to assess the safety and efficacy of IFN-γ receptor-deficient CAR-T cells in patients with solid tumors.
• Published in Science Translational Medicine, the study was conducted by teams at Massachusetts General Hospital’s Krantz Family Center for Cancer Research.