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Review

In Vivo Engineered CAR-T Cell Therapy: Lessons Built from COVID-19 mRNA Vaccines

by
Sikun Meng
1,
Tomoaki Hara
1,
Yutaka Miura
2,
Yasuko Arao
1,
Yoshiko Saito
1,
Kana Inoue
1,
Takaaki Hirotsu
3,
Andrea Vecchione
4,
Taroh Satoh
5 and
Hideshi Ishii
1,*
1
Department of Medical Data Science, Center of Medical Innovation and Translational Research, Osaka University Graduate School of Medicine, Yamadaoka 2-2, Suita, Osaka 565-0871, Japan
2
Laboratory for Chemistry and Life Science, Institute of Integrated Research, Institute of Science Tokyo, 4259 Nagatsutacho, Midori-ku, Yokohama 226-8501, Japan
3
Hirotsu Bio Science Inc., Chiyoda-Ku, Tokyo 102-0094, Japan
4
Department of Clinical and Molecular Medicine, University of Rome “Sapienza”, Santo Andrea Hospital, Via di Grottarossa, 1035, 00189 Rome, Italy
5
Center for Cancer Genomics and Precision Medicine, Osaka University Hospital, Yamadaoka 2-2, Suita, Osaka 565-0871, Japan
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2025, 26(7), 3119; https://doi.org/10.3390/ijms26073119
Submission received: 11 February 2025 / Revised: 13 March 2025 / Accepted: 26 March 2025 / Published: 28 March 2025
(This article belongs to the Special Issue Advances and Perspectives in Molecular Tumor Therapy)
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Abstract

Chimeric antigen receptor T cell (CAR-T) therapy has revolutionized cancer immunotherapy but continues to face significant challenges that limit its broader application, such as antigen targeting, the tumor microenvironment, and cell persistence, especially in solid tumors. Meanwhile, the global implementation of mRNA vaccines during the COVID-19 pandemic has highlighted the transformative potential of mRNA and lipid nanoparticle (LNP) technologies. These innovations, characterized by their swift development timelines, precise antigen design, and efficient delivery mechanisms, provide a promising framework to address some limitations of CAR-T therapy. Recent advancements, including mRNA-based CAR engineering and optimized LNP delivery, have demonstrated the capacity to enhance CAR-T efficacy, particularly in the context of solid tumors. This review explores how mRNA-LNP technology can drive the development of in vivo engineered CAR-T therapies to address current limitations and discusses future directions, including advancements in mRNA design, LNP optimization, and strategies for improving in vivo CAR-T functionality and safety. By bridging these technological insights, CAR-T therapy may evolve into a versatile and accessible treatment paradigm across diverse oncological landscapes.
Keywords: CAR-T therapy; mRNA vaccines; mRNA technology; lipid nanoparticles; immune response regulation CAR-T therapy; mRNA vaccines; mRNA technology; lipid nanoparticles; immune response regulation

Share and Cite

MDPI and ACS Style

Meng, S.; Hara, T.; Miura, Y.; Arao, Y.; Saito, Y.; Inoue, K.; Hirotsu, T.; Vecchione, A.; Satoh, T.; Ishii, H. In Vivo Engineered CAR-T Cell Therapy: Lessons Built from COVID-19 mRNA Vaccines. Int. J. Mol. Sci. 2025, 26, 3119. https://doi.org/10.3390/ijms26073119

AMA Style

Meng S, Hara T, Miura Y, Arao Y, Saito Y, Inoue K, Hirotsu T, Vecchione A, Satoh T, Ishii H. In Vivo Engineered CAR-T Cell Therapy: Lessons Built from COVID-19 mRNA Vaccines. International Journal of Molecular Sciences. 2025; 26(7):3119. https://doi.org/10.3390/ijms26073119

Chicago/Turabian Style

Meng, Sikun, Tomoaki Hara, Yutaka Miura, Yasuko Arao, Yoshiko Saito, Kana Inoue, Takaaki Hirotsu, Andrea Vecchione, Taroh Satoh, and Hideshi Ishii. 2025. "In Vivo Engineered CAR-T Cell Therapy: Lessons Built from COVID-19 mRNA Vaccines" International Journal of Molecular Sciences 26, no. 7: 3119. https://doi.org/10.3390/ijms26073119

APA Style

Meng, S., Hara, T., Miura, Y., Arao, Y., Saito, Y., Inoue, K., Hirotsu, T., Vecchione, A., Satoh, T., & Ishii, H. (2025). In Vivo Engineered CAR-T Cell Therapy: Lessons Built from COVID-19 mRNA Vaccines. International Journal of Molecular Sciences, 26(7), 3119. https://doi.org/10.3390/ijms26073119

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