| First Author | Zhang G | Year | 2025 |
| Journal | Nat Commun | Volume | 16 |
| Issue | 1 | Pages | 8088 |
| PubMed ID | 40883321 | Mgi Jnum | J:391126 |
| Mgi Id | MGI:8242037 | Doi | 10.1038/s41467-025-63427-w |
| Citation | Zhang G, et al. (2025) GD2T(IF) cells as a platform for single-dose and long-term delivery of biologics. Nat Commun 16(1):8088 |
| abstractText | 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. |
