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Archive > Volume 33 Issue 6 > 2026,33(6):602-610. DOI:10.3872/j.issn.1007-385X.2026.06.002 Prev Next
Editorial
Lentiviral delivery for in vivo CAR-T cell generation: targeted delivery strategies and research progress
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Abstract:
[Abstract] Chimeric antigen receptor T (CAR-T) cell therapy has shown remarkable efficacy in hematologic malignancies, but conventional ex vivo manufacturing is limited by procedural complexity, long production cycles, and high cost. In vivo CAR-T cell generation directly reprograms T cells in patients through gene-delivery vectors and may simplify manufacturing and improve accessibility. Lentiviral vectors offer relatively large payload capacity, stable genomic integration, and mature manufacturing systems; however, broad tropism of native or pseudotyped envelopes may cause off-target transduction and safety risks. This review summarizes envelope pseudotyping and receptor- detargeting strategies based on the envelopes of vesicular stomatitis virus glycoprotein (VSV-G), Cocal virus glycoprotein (COCV-G), Sindbis virus, measles virus, and Nipah virus; discusses the selection of CD3, TCR, CD4, CD8, and CD7 as targeting receptors and the integration of CD2/CD28 costimulatory signals; and reviews preclinical studies and early clinical translation. Available evidence indicates that targeted lentiviral vectors can generate functional antitumor CAR-T cells in vivo, although insertional mutagenesis, off-target transduction, immunogenicity, dose control, and scalable manufacturing remain major challenges. This review provides a technical reference for the design and translation of next-generation in vivo CAR-T cell delivery systems.
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