GD2TIF cells as a platform for single-dose and long-term delivery of biologics

Guangyue Zhang, Na Yin and Min Peng ()
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Guangyue Zhang: Tsinghua University
Na Yin: Tsinghua University
Min Peng: Tsinghua University

Nature Communications, 2025, vol. 16, issue 1, 1-13

Abstract: 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 GD2TIF cells. These GD2TIF 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 GD2TIF cells producing leptin effectively and durably corrected leptin deficiency. Furthermore, a single infusion of GD2TIF cells secreting GLP-1 prevented obesity and diabetes in mice fed on a high-fat diet. The longevity, safety, and adaptability of GD2TIF cells suggest their potential as a general platform for long-term delivery of biologics, offering durable therapeutic efficacy with a single infusion.

Date: 2025
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DOI: 10.1038/s41467-025-63427-w

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