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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.
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Genes & Diseases publishes rigorously peer-reviewed and high quality original articles and authoritative reviews that focus on the molecular bases of human diseases. Emphasis is placed on hypothesis-driven, mechanistic studies relevant to pathogenesis and/or experimental therapeutics of human diseases. The journal has worldwide authorship, and a broad scope in basic and translational biomedical research of molecular biology, molecular genetics, and cell biology, including but not limited to cell proliferation and apoptosis, signal transduction, stem cell biology, developmental biology, gene regulation and epigenetics, cancer biology, immunity and infection, neuroscience, disease-specific animal models, gene and cell-based therapies, and regenerative medicine.
Scopus CiteScore: 8.4
Impact Factor: 9.4
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Reference
Zhiqiang Song, Yi Zhou, Binbin Wang, Yuke Geng, Gusheng Tang, Yang Wang, Jianmin Yang, In vivo production of CAR T cell: Opportunities and challenges, Genes & Diseases, Volume 12, Issue 6, 2025,
101612, https://doi.org/10.1016/j.gendis.2025.101612
Funding Information:
Science and Technology Commission of Shanghai Municipality (China) 24YF2758000
National Natural Science Foundation of China 82270202
National Natural Science Foundation of China 82300257
National Natural Science Foundation of China 82470190
Medical-enterprise Integration Innovation and Collaboration Project (China) SHDC2023CRT005
Youth Start-up Foundation of the First Affiliated Hospital of Second Military Medical University (China) 2022QN067
Changhai Hospital "Changfeng" Project (China)
Changzheng Hospital "Pyramid Talent" Project (China)
END
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