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Current status and regulatory perspective of chimeric antigen receptor-modified T cell therapeutics

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Abstract

Chimeric antigen receptor-modified T cells (CAR-T) have emerged as a new modality for cancer immunotherapy due to their potent efficacy against terminal cancers. CAR-Ts are reported to exert higher efficacy than monoclonal antibodies and antibody–drug conjugates, and act via mechanisms distinct from T cell receptor-engineered T cells. These cells are constructed by transducing genes encoding fusion proteins of cancer antigen-recognizing single-chain Fv linked to intracellular signaling domains of T cell receptors. CAR-Ts are classified as first-, second- and third-generation, depending on the intracellular signaling domain number of T cell receptors. This review covers the current status of CAR-T research, including basic proof-of-concept investigations at the cell and animal levels. Currently ongoing clinical trials of CAR-T worldwide are additionally discussed. Owing to the lack of existing approved products, several unresolved concerns remain with regard to safety, efficacy and manufacturing of CAR-T, as well as quality control issues. In particular, the cytokine release syndrome is the major side-effect impeding the successful development of CAR-T in clinical trials. Here, we have addressed the challenges and regulatory perspectives of CAR-T therapy.

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Acknowledgments

This research was supported by a grant (15172MFDS163) from Ministry of Food and Drug Safety in 2015.

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Authors and Affiliations

  1. College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea

    Mi-Gyeong Kim, Dongyoon Kim, Min Joung Choi & Yu-Kyoung Oh

  2. Advanced Therapy Product Research Division, National Institute of Food and Drug Safety, Cheongju, Chungcheongbuk-do, Republic of Korea

    Soo-Kyung Suh & Zewon Park

  3. Cell and Gene Therapeutics Division, National Institute of Food and Drug Safety, Cheongju, Chungcheongbuk-do, Republic of Korea

    Min Joung Choi

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  1. Mi-Gyeong Kim
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Kim, MG., Kim, D., Suh, SK. et al. Current status and regulatory perspective of chimeric antigen receptor-modified T cell therapeutics. Arch. Pharm. Res. 39, 437–452 (2016). https://doi.org/10.1007/s12272-016-0719-7

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