Adoptive immune cell therapies, particularly CAR-T-cell therapy, have achieved remarkable success in hematological malignancies. However, conventional treatment requires cell collection, ex vivo genetic modification, expansion, quality control, and reinfusion, resulting in long manufacturing times, high costs, and limited accessibility.
In vivo immune cell engineering provides a potential alternative to conventional ex vivo cell manufacturing by delivering genetic cargos directly to defined immune-cell populations within the body. Viral vectors, lipid nanoparticles and other delivery platforms can be used to reprogram various immune cells such as T cells and macrophages in situ, thereby inducing or regulating therapeutic immune functions.
This review provides an integrated overview of in vivo immune cell engineering, from immune-cell targeting and delivery-platform design to emerging therapeutic applications. It contrasts viral vectors, which generally support durable gene expression, with non-viral systems that enable more transient and potentially tunable programming, and highlights recent advances in cancer, autoimmune diseases, and other indications. The review further discusses the major barriers to clinical translation, including cell-type specificity, off-target delivery and editing, immunogenicity, expression control, safety, scalable manufacturing, and regulatory standardization.
By integrating progress in immunology, gene delivery, genome editing, and biomaterials, the review provides a concise framework for understanding the transition of in vivo immune cell engineering from experimental research toward clinical application. The work entitled “In vivo immune cell engineering from bench to clinical reality” was published in Pharmaceutical Science Advances (published on July 8, 2026).
DOI：10.1016/j.pscia.2026.100131