Frontiers in Immunology · Published 2026-08-04 · DOI 10.3389/fimmu.2026.1841160
He Wang, Guangmei Qiao, Ming Ma, Hailong Zhao, Lin Luo, Ting Liu
Ex vivo CAR-T changed cancer care, but its made-to-order manufacturing keeps too many patients waiting. In vivo CAR-T takes a different path: deliver the genetic blueprint to a patient’s own immune cells and let the body build the therapy. In this review, we compare the leading delivery platforms—retargeted lentiviral vectors, engineered AAVs, LNPs (mRNA/circRNA), polymeric nanoparticles, and bioinspired systems—through the lenses of specificity, expression durability, redosing, manufacturability, immunogenicity, safety, and clinical maturity. Early human observations in hematologic malignancies and autoimmune disease show what’s possible; solid-tumor progress is still largely preclinical. Key translational challenges include: off-target transduction and murky biodistribution, liver-skewed exposure for non-viral systems, integration risk for durable vectors, repeat-dose immunity, CMC consistency, and regulatory fit. We outline a practical roadmap—quantitative biodistribution and potency, cargo-tuned persistence, receptor-aware targeting, robust CMC, and indication-specific risk–benefit—to support reproducible and clinically interpretable therapeutic development.
Abstract from DOAJ. Public domain (CC0 1.0).
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Wang, H., Qiao, G., Ma, M., et al. (2026). Delivery platforms for in vivo CAR-T engineering. Frontiers in Immunology. https://doi.org/10.3389/fimmu.2026.1841160