RB-340

RB-340 is a next-generation, CRISPRi‑enhanced HER2‑targeted CAR-T cell therapy being developed by Refuge Biotechnologies for the treatment of solid tumors. It is designed so that CAR signaling against HER2 conditionally downregulates programmed cell death protein 1 (PD-1) expression via a CRISPR interference circuit, thereby reducing T‑cell exhaustion and enhancing persistence and proliferation in the tumor microenvironment.[1][3][5] Preclinical studies of the closely related construct RB-340-1 demonstrated improved expansion, higher production of homeostatic cytokines, prolonged in vivo persistence, and superior antitumor activity against HER2‑positive FaDu oropharyngeal cancer xenografts compared with conventional HER2 CAR-T cells.[1][7] Clinical development of RB-340 is planned in solid tumors, with an IND filing indicated but not yet reflecting an active clinical trial.[3][10]