Streamlining CAR T cell production through in vivo therapeutic strategies

This review article highlights the transformative potential of in vivo CAR T cell therapy in addressing the limitations of traditional CAR T cell production. This innovative approach could revolutionize cancer treatment, offering a more efficient, scalable, and cost-effective alternative to conventional methods.

CAR T cell therapy has shown remarkable success in treating hematological malignancies; however, current production methods are laborious, time-consuming, and expensive. Traditional in vitro CAR T cell production typically requires 2–3 weeks and involves complex processes, including T cell isolation, activation, genetic modification, expansion, and quality control. This time-consuming method is further complicated by the need for personalized production, limiting its application in rapidly progressing diseases.

The in vivo approach represents a breakthrough by eliminating the need for extensive laboratory manipulation. Instead of manufacturing CAR T cells outside the body, this method involves direct delivery of CAR constructs into T cells within the patient's body. The process leverages viral and nonviral vectors to facilitate the genetic modification of T cells, enabling them to effectively target and eliminate cancer cells.

One of the key advantages of in vivo CAR T cell production is its potential for scalability and reduced costs. Unlike the "one patient, one batch" model of in vitro methods, in vivo techniques can generate "off-the-shelf" CAR T cell products, allowing for mass production and broader accessibility. Additionally, this method preserves T cell functionality, enhancing therapeutic efficacy compared to in vitro-produced CAR T cells, which often experience functional impairment.

The review underscores that in vivo CAR T cell therapy is particularly promising for rapidly progressing cancers due to its quick response time. Moreover, the use of nanoparticle-based systems and viral vectors like lentiviral (LV) and adeno-associated virus (AAV) ensures efficient gene transfer and stable CAR expression. These vectors have demonstrated high transfection rates and low safety risks compared to earlier methods.

However, the approach is not without challenges. The potential for off-target effects, immunogenicity, and the risk of insertional mutations remains a critical area of investigation. Addressing these concerns will be vital for the widespread clinical adoption of in vivo CAR T cell therapies. Moreover, balancing cost-effectiveness with high transfection efficiency will determine the practical viability of this technique.