Abstract
In vivo Chimeric Antigen Receptor (CAR)-T cell therapy reprograms a patient's own T cells directly inside the body, bypassing the complex and costly traditional manufacturing process. This is achieved by systemically delivering viral or non-viral vectors that genetically modify endogenous T lymphocytes to produce functional CAR-T cells de novo. By eliminating ex vivo cell processing, this strategy can simplify workflows, reduce costs, improve accessibility, and allow faster treatment. Key delivery platforms include engineered lentiviral and adeno-associated viral (AAV) vectors for lasting CAR expression and targeted lipid nanoparticles (LNPs) for transient mRNA delivery. Emerging technologies like biomaterial scaffolds and ultrasound stimulation further enable localized and spatiotemporally controlled T cell engineering. Clinically, early trials in relapsed/refractory multiple myeloma and B-cell malignancies have shown strong antitumor responses, even without preconditioning chemotherapy. Remaining challenges comprise achieving precise T cell targeting, overcoming the immunosuppressive tumor microenvironment, preventing antigen escape, and managing safety risks such as vector genotoxicity or LNP reactogenicity. Future translation will depend on combining synergistic regimens, refining vector design, and implementing tunable safety controls. The aim of the study is to highlight how in vivo CAR-T therapy is evolving from concept to clinical reality, poised to redefine adoptive cell therapy as a scalable and widely applicable pharmacologic intervention.