In vivo CAR-T therapy: Delivery systems and beyond for addressing expression, persistence, and safety challenges
Year: 2026
Type: review
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.
Source: Acta Pharmaceutica Sinica B
Authors: Ziyi Zhang, Xingxing Shang, Tong Zhang, Dianwen Ju
Institution: Fudan University
Language: English
Topic: CAR-T cell therapy research
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,600
OpenAlex ID: W7204801574