In vivo CAR-T therapy: Delivery systems and beyond for addressing expression, persistence, and safety challenges
- 1School of Pharmaceutical Sciences & Minhang Hospital, Fudan University, Shanghai 200433, China
Abstract
The clinical translation of ex vivo CAR-T therapy is constrained by its complex manufacturing processes, limited treatment accessibility, and the toxicities associated with lymphodepleting chemotherapy. In vivo CAR-T strategies, which utilize viral or non-viral vectors to reprogram a patient's T cells directly in situ genetically, offer a promising alternative. This review provides a systematic examination of the critical barriers impeding the advancement of in vivo CAR-T therapy. We first summarize the factors influencing the targeting ability of both the delivery system and the CAR molecule. As for the vectors, we detail how the composition and physicochemical properties of LNPs shift their tropism from the liver to the spleen and provide a critical comparison of active targeting strategies based on different T-cell surface antigens. As for the CAR molecule, target selection is primarily dictated by the intended disease. Furthermore, we discuss the determinants of poor CAR-T cell persistence, including unstable mRNA payloads and exhaustion-associated signaling pathways. Addressing the challenges of solid tumor treatment, we dissect the multifaceted role of the tumor microenvironment. Finally, this review illustrates the mechanisms underlying overactivation and immunogenicity triggered by both viral and non-viral vector systems.
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BibTeX
@article{zhang2026vivo,
title = {{In vivo CAR-T therapy: Delivery systems and beyond for addressing expression, persistence, and safety challenges}},
author = {Ziyi Zhang and Xingxing Shang and Tong Zhang and Dianwen Ju},
journal = {Acta pharmaceutica Sinica. B},
year = {2026},
month = aug,
doi = {10.1016/j.apsb.2026.08.030},
url = {https://europepmc.org/article/PMC/PMC13729517},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - In vivo CAR-T therapy: Delivery systems and beyond for addressing expression, persistence, and safety challenges
AU - Ziyi Zhang
AU - Xingxing Shang
AU - Tong Zhang
AU - Dianwen Ju
PY - 2026
DA - 2026/08/31
JO - Acta pharmaceutica Sinica. B
DO - 10.1016/j.apsb.2026.08.030
UR - https://europepmc.org/article/PMC/PMC13729517
AB - The clinical translation of ex vivo CAR-T therapy is constrained by its complex manufacturing processes, limited treatment accessibility, and the toxicities associated with lymphodepleting chemotherapy. In vivo CAR-T strategies, which utilize viral or non-viral vectors to reprogram a patient's T cells directly in situ genetically, offer a promising alternative. This review provides a systematic examination of the critical barriers impeding the advancement of in vivo CAR-T therapy. We first summarize the factors influencing the targeting ability of both the delivery system and the CAR molecule. As for the vectors, we detail how the composition and physicochemical properties of LNPs shift their tropism from the liver to the spleen and provide a critical comparison of active targeting strategies based on different T-cell surface antigens. As for the CAR molecule, target selection is primarily dictated by the intended disease. Furthermore, we discuss the determinants of poor CAR-T cell persistence, including unstable mRNA payloads and exhaustion-associated signaling pathways. Addressing the challenges of solid tumor treatment, we dissect the multifaceted role of the tumor microenvironment. Finally, this review illustrates the mechanisms underlying overactivation and immunogenicity triggered by both viral and non-viral vector systems.
SN - 2211-3835
SN - 2211-3843
ER -