GD2T_IF cells as a platform for single-dose and long-term delivery of biologics.

Abstract

The efficacy of biologics, such as peptide and protein drugs, is often limited by their short half-lives in vivo, necessitating repeated infusions to maintain therapeutic effects. Here, we demonstrate that long-lived CAR T cells can be leveraged as a versatile platform for long-term delivery of biologics. Our recent findings show that the depletion of BCOR and ZC3H12A induces GD2 CAR T cells into an immortal-like and functional state, which we have termed GD2T_IF cells. These GD2T_IF cells expanded in immunocompetent mice without the need for chemotherapeutic conditioning and persisted as a polyclonal population, safely and almost indefinitely. In leptin-deficient ob/ob mice, a single infusion of GD2T_IF cells producing leptin effectively and durably corrected leptin deficiency. Furthermore, a single infusion of GD2T_IF cells secreting GLP-1 prevented obesity and diabetes in mice fed on a high-fat diet. The longevity, safety, and adaptability of GD2T_IF cells suggest their potential as a general platform for long-term delivery of biologics, offering durable therapeutic efficacy with a single infusion.