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CAR-T cell therapy in AML: recent progress and future perspectives

  • Progress in Hematology
  • Recent progress in the molecular pathophysiology and treatment of acute myeloid leukemia
  • Published:
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Abstract

Despite several small-molecule drugs that have revolutionized the current treatment strategy for acute myeloid leukemia (AML), hematopoietic stem cell transplantation remains the only curative treatment in most cases to date. Chimeric antigen receptor (CAR)-T cell therapy is one of the most promising next-generation cancer therapies for hematological malignancies and is clinically available for treatment of AML. However, develo** AML-targeted CAR-T therapy is challenging because of the heterogeneity of target antigen expression across leukemic cells and patients, the difficulty in excluding on-/off-target tumor effects, and the immunosuppressive tumor microenvironment. To date, various targets, including CD33, NKG2D, CD123, CLL-1, and CD7, have been actively studied for CAR-T cells. Although no CAR-T cell products are close to practical use, several clinical trials have shown promising results, particularly for CAR-T cells targeting CLL-1 or CD123. Meanwhile, research exploring the ideal target for AML-targeted CAR-T therapy continues. Furthermore, as collecting autologous lymphocytes from patients with AML is difficult, development of off-the-shelf CAR-T products is being actively pursued. This review discusses the challenges in AML-targeted CAR-T cell therapy development from the perspectives of target antigen characteristics and AML-specific on-target/off-tumor toxicity. Moreover, it discusses the clinical development and prospects of AML-targeting CAR-T cells.

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Acknowledgements

The authors also thank ENAGO for the English proofreading.

Funding

This work was supported by the Japan Agency for Medical Research and Development (AMED) (23ck0106821h0001 and 23ae0201006h000).

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Authors and Affiliations

  1. Department of Pediatrics, Shinshu University School of Medicine, Asahi 3-1-1, Matsumoto, Nagano, 390-8621, Japan

    Shoji Saito & Yozo Nakazawa

  2. Center for Advanced Research of Gene and Cell Therapy, Shinshu University, Matsumoto, Japan

    Shoji Saito & Yozo Nakazawa

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  1. Shoji Saito
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  2. Yozo Nakazawa
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Correspondence to Shoji Saito.

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SS declares no competing interests regarding this work. YN has the following competing interests: leadership position/Advisory role, A-SEEDS Co., Ltd.; Stock ownership or options, A-SEEDS Co., Ltd.; Research founding: BrightPath BioTherapeutics Co., Ltd., AGC Inc., Toshiba Corp., Daiichi Sankyo Co., Ltd., Noile-Immune Biotech Inc., Bourbon Corp. & CSTI Inc.

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Saito, S., Nakazawa, Y. CAR-T cell therapy in AML: recent progress and future perspectives. Int J Hematol (2024). https://doi.org/10.1007/s12185-024-03809-w

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