In-vivo CAR-T Cell Engineering: A Narrative Review of Emerging Delivery Strategies and Their Potential Future Impact on Accessibility
TL;DR
If in-vivo CAR-T therapy approaches continue to mature, they may offer a more scalable, cost-effective, and accessible alternative to traditional ex vivo CAR-T therapy, though this remains a projected rather than demonstrated benefit.
Abstract
Chimeric antigen receptor T-cell (CAR-T) therapy has emerged as a groundbreaking advancement in cancer immunotherapy, progressively improving over decades and producing remarkable clinical outcomes. This review examines the evolution of CAR-T cell therapy by comparing ex vivo and newer in-vivo approaches, evaluating the four primary delivery vehicles used for in-vivo CAR-T therapy, and discussing their implications for safety, scalability, accessibility and future development. Although ex vivo CAR-T therapy has demonstrated substantial clinical success, its complex manufacturing process, high cost, prolonged production time, and reliance on specialized facilities limit patient access worldwide. In contrast, in-vivo CAR-T therapy genetically reprograms T cells directly within the body, eliminating external manipulation of T cells and thus many of the logistical barriers associated with ex vivo manufacturing. Four primary delivery vehicles have shown immense progress within-vivo CAR-T cell therapy: lentiviral vectors, lipid nanoparticles, polymeric nanoparticles, and virus-like particles. Each delivery platform offers distinct advantages and limitations in terms of efficacy, safety, and scalability. Most evidence for in-vivo CAR-T therapy to date comes from preclinical and early-phase studies; if these approaches continue to mature, they may offer a more scalable, cost-effective, and accessible alternative to traditional ex vivo CAR-T therapy, though this remains a projected rather than demonstrated benefit.