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piggyBac-transposon-mediated CAR-T cells for the treatment of hematological and solid malignancies

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Abstract

Since the introduction of the use of chimeric antigen receptor T-cell therapy (CAR-T therapy) dramatically changed the therapeutic strategy for B cell tumors, various CAR-T cell products have been developed and applied to myeloid and solid tumors. Although viral vectors have been widely used to produce genetically engineered T cells, advances in genetic engineering have led to the development of methods for producing non-viral, gene-modified CAR-T cells. Recent progress has revealed that non-viral CAR-T cells have a significant impact not only on the simplicity of the production process and the accessibility of non-viral vectors but also on the function of the cells themselves. In this review, we focus on piggyBac-transposon-based CAR-T cells among non-viral, gene-modified CAR-T cells and discuss their characteristics, preclinical development, and recent clinical applications.

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Acknowledgements

The authors thank Drs. Miyuki Tanaka, Shoji Saito, Koichi Hirabayashi, Aiko Hasegawa, Yoichi Inada, Konomi Morita, Kayoko Nakamura, Hiroshi Kubo, Akimasa Tomida, and Masaya Suematsu for their tremendous work in the development of PB-based CAR-T cells. The authors also thank Editage for proofreading the manuscript. This work was supported by the Japan Agency for Medical Research and Development (AMED; 22ck0106659s0102, 22ck0106574h0003), and JSPS KAKENHI (20K07461).

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Authors and Affiliations

  1. Innovative Research and Liaison Organization, Shinshu University, 3-1-1, Asahi, Matsumoto, Nagano, Japan

    Shigeki Yagyu

  2. Center for Advanced Research of Gene and Cell Therapy, Shinshu University, 3-1-1, Asahi, Matsumoto, Nagano, Japan

    Shigeki Yagyu & Yozo Nakazawa

  3. Department of Pediatrics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachihirokoji, Kamigyo-ku, Kyoto, Japan

    Shigeki Yagyu

  4. Department of Pediatrics, Shinshu University School of Medicine, 3-1-1, Asahi, Matsumoto, Nagano, Japan

    Yozo Nakazawa

  5. Institute for Biomedical Sciences, Interdisciplinary Cluster for Cutting Edge Research, Shinshu University, 3-1-1, Asahi, Matsumoto, Nagano, Japan

    Yozo Nakazawa

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  1. Shigeki Yagyu
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Correspondence to Shigeki Yagyu.

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Shigeki Yagyu is the chief executive officer of A-SEEDS Inc. Yozo Nakazawa is the executive director of A-SEEDS Inc. with equity. Shigeki Yagyu and Yozo Nakazawa have patent applications in the field of adoptive cell therapy for cancer.

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Yagyu, S., Nakazawa, Y. piggyBac-transposon-mediated CAR-T cells for the treatment of hematological and solid malignancies. Int J Clin Oncol 28, 736–747 (2023). https://doi.org/10.1007/s10147-023-02319-9

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