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Targeting FLT3 by chimeric antigen receptor T cells for the treatment of acute myeloid leukemia

Leukemia volume 31, pages 1830–1834 (2017)Cite this article

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Despite a broad understanding of the molecular and genetic complexity of acute myeloid leukemia (AML), the only immune therapy known to provide a significant improvement in outcome over standard chemotherapy is allogeneic hematopoietic stem cell transplant (HSCT). However, many patients, especially the elderly, are not eligible for allogeneic HSCT because of the rigorous conditioning and complications from the treatment, including serious and sometimes fatal graft-versus-host disease (GVHD). The 5-year survival rates in elderly AML patients (⩾65 years) are below 10%.1 Moreover, certain molecular aberrations associated with AML, such as the FLT3 internal tandem duplication (ITD) and FLT3 point mutations have an especially adverse prognosis and a high probability of relapse.2, 3, 4 Therefore, novel approaches for the treatment of AML represent an unmet therapeutic need.

Recently, the genetic modification of T cells with chimeric antigen receptors (CARs) that directly target tumor-associated antigens has shown success in the clinic when targeting CD19 in acute lymphoblastic leukemia (ALL) and chronic lymphocytic leukemia (CLL).5 However, identification of tumor-associated surface antigens that can be targeted by CAR immune cells for the treatment of cancer such as AML has proven to be challenging.

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Acknowledgements

This project was supported in part by a grant from the Gabrielle’s Angel Cancer Research Foundation as well as grants from the National Institutes of Health (CA155521, CA210087, CA068458, CA095426, CA185301, and P30 CA16058). This project was also supported in part by an American Cancer Society Research Scholar Grant RSG-14-243-01-LIB and a grant from the Leukemia & Lymphoma Society. The authors are grateful to David Lucas and Donna Bucci at the Leukemia Tissue Bank Shared Resource of the OSU Comprehensive Cancer Center and James Cancer Hospital for providing AML patient samples.

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Authors and Affiliations

  1. Division of Hematology, Department of Internal Medicine, College of Medicine, The Ohio State University, Columbus, OH, USA

    L Chen, S Devine, M A Caligiuri & J Yu

  2. The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA

    L Chen, H Mao, J Chu, S Devine, M A Caligiuri & J Yu

  3. Department of Bioinformatics, Center for Biostatistics, The Ohio State University, Columbus, OH, USA

    J Zhang

  4. The James Cancer Hospital and Solove Research Institute, Columbus, OH, USA

    S Devine, M A Caligiuri & J Yu

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  1. L Chen
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  2. H Mao
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Correspondence to J Yu.

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Chen, L., Mao, H., Zhang, J. et al. Targeting FLT3 by chimeric antigen receptor T cells for the treatment of acute myeloid leukemia. Leukemia 31, 1830–1834 (2017). https://doi.org/10.1038/leu.2017.147

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