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<p>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<sub>IF</sub> cells. These GD2T<sub>IF</sub> cells expanded in immunocompetent mice without the need for chemotherapeutic conditioning and persisted as a polyclonal population, safely and almost indefinitely. In leptin-deficient <i>ob/ob</i> mice, a single infusion of GD2T<sub>IF</sub> cells producing leptin effectively and durably corrected leptin deficiency. Furthermore, a single infusion of GD2T<sub>IF</sub> cells secreting GLP-1 prevented obesity and diabetes in mice fed on a high-fat diet. The longevity, safety, and adaptability of GD2T<sub>IF</sub> cells suggest their potential as a general platform for long-term delivery of biologics, offering durable therapeutic efficacy with a single infusion.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年8月29日

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  • Guangyue Zhang,
  • Na Yin,
  • Min Peng

摘要

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.