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Harnessing the Immune System Against Leukemia: Monoclonal Antibodies and Checkpoint Strategies for AML

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  • First Online:
Immunotherapy

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 995))

Abstract

Acute myeloid leukemia (AML) is the most common leukemia among adults and is associated with a poor prognosis, especially in patients with adverse prognostic factors, older age, or relapsed disease. The last decade has seen a surge in successful immune-based therapies in various solid tumors; however, the role of immune therapies in AML remains poorly defined. This chapter describes the rationale, clinical data, and toxicity profiles of immune-based therapeutic modalities in AML including naked and conjugated monoclonal antibodies, bispecific T-cell engager antibodies, chimeric antigen receptor (CAR)-T cells, and checkpoint blockade via blockade of PD1/PDL1 or CTLA4. Monoclonal antibodies commonly used in AML therapy target highly expressed “leukemia” surface antigens and include (1) naked antibodies against common myeloid markers such as anti-CD33 (e.g., lintuzumab), (2) antibody-drug conjugates linked to either, (a) a highly potent toxin such as calicheamicin, pyrrolobenzodiazepine, maytansine, or others in various anti-CD33 (gemtuzumab ozogamicin, SGN 33A), anti-123 (SL-401), and anti-CD56 (lorvotuzumab mertansine) formulations, or (b) radioactive particles, such as 131I, 213Bi, or 225Ac-labeled anti-CD33 or CD45 antibodies. Novel monoclonal antibodies that recruit and promote proximity-induced cytotoxicity of tumor cells by T cells (bispecific T-cell engager [BiTE] such as anti CD33/CD3, e.g., AMG 330) or block immune checkpoint pathways such as CTLA4 (e.g., ipilimumab) or PD1/PD-L1 (e.g., nivolumab) unleashing the patients T cells to fight leukemic cells are being evaluated in clinical trials in patients with AML. The numerous ongoing clinical trials with immunotherapies in AML will improve our understanding of the biology of AML and allow us to determine the best approaches to immunotherapy in AML.

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Acknowledgements

This review was supported in part by the MD Anderson Cancer Centre Support Grant (CCSG) CA016672.

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Authors and Affiliations

  1. Department of Leukemia, MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA

    Lucia Masarova, Hagop Kantarjian, Guillermo Garcia-Mannero, Farhad Ravandi & Naval Daver

  2. Immunotherapy Platform, MD Anderson Cancer Center, Houston, TX, USA

    Padmanee Sharma

Authors
  1. Lucia Masarova
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  2. Hagop Kantarjian
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  3. Guillermo Garcia-Mannero
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  4. Farhad Ravandi
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  5. Padmanee Sharma
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  6. Naval Daver
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Corresponding author

Correspondence to Naval Daver .

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Editors and Affiliations

  1. MD Anderson Cancer Center, University of Texas, Houston, Texas, USA

    Aung Naing

  2. Baylor College of Medicine-Texas Children’s Hospital, Houston, Texas, USA

    Joud Hajjar

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Author Contributions

 LM, HK, GGM, FR, PS, and ND collected and reviewed the data and wrote the paper. All authors participated in the discussion, have reviewed, and approved the current version of the manuscript.

Naval Daver is responsible for the overall content as guarantor.

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Masarova, L., Kantarjian, H., Garcia-Mannero, G., Ravandi, F., Sharma, P., Daver, N. (2017). Harnessing the Immune System Against Leukemia: Monoclonal Antibodies and Checkpoint Strategies for AML. In: Naing, A., Hajjar, J. (eds) Immunotherapy. Advances in Experimental Medicine and Biology, vol 995. Springer, Cham. https://doi.org/10.1007/978-3-319-53156-4_4

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