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Int J Mol Sci. 2017 Jul 31;18(8). pii: E1660. doi: 10.3390/ijms18081660.

Immunotherapeutic Concepts to Target Acute Myeloid Leukemia: Focusing on the Role of Monoclonal Antibodies, Hypomethylating Agents and the Leukemic Microenvironment.

Author information

1
Department of Medicine, Division of Hematology/Oncology, Indiana University School of Medicine, Indianapolis, IN 46202, USA. obgbolah@iu.edu.
2
Department of Medicine, Section of Hematology, Yale University School of Medicine, New Haven, CT 06510, USA. amer.zeidan@yale.edu.
3
Department of Medicine, Section of Hematology, Yale University School of Medicine, New Haven, CT 06510, USA. maximilian.stahl@yale.edu.
4
Department of Medicine, Bone Marrow and Stem Cell Transplantation, Indiana University School of Medicine, Indianapolis, IN 46202, USA. mabuzaid@iu.edu.
5
Department of Medicine, Bone Marrow and Stem Cell Transplantation, Indiana University School of Medicine, Indianapolis, IN 46202, USA. ssfarag@iu.edu.
6
Wells Center for Pediatric Research, Riley Hospital for Children, Indiana University School of Medicine, Indianapolis, IN 46202, USA. sophpacz@iu.edu.
7
Department of Medicine, Division of Hematology/Oncology, Indiana University School of Medicine, Indianapolis, IN 46202, USA. hkonig@iupui.edu.

Abstract

Intensive chemotherapeutic protocols and allogeneic stem cell transplantation continue to represent the mainstay of acute myeloid leukemia (AML) treatment. Although this approach leads to remissions in the majority of patients, long-term disease control remains unsatisfactory as mirrored by overall survival rates of approximately 30%. The reason for this poor outcome is, in part, due to various toxicities associated with traditional AML therapy and the limited ability of most patients to tolerate such treatment. More effective and less toxic therapies therefore represent an unmet need in the management of AML, a disease for which therapeutic progress has been traditionally slow when compared to other cancers. Several studies have shown that leukemic blasts elicit immune responses that could be exploited for the development of novel treatment concepts. To this end, early phase studies of immune-based therapies in AML have delivered encouraging results and demonstrated safety and feasibility. In this review, we discuss opportunities for immunotherapeutic interventions to enhance the potential to achieve a cure in AML, thereby focusing on the role of monoclonal antibodies, hypomethylating agents and the leukemic microenvironment.

KEYWORDS:

acute myeloid leukemia; hypomethylating agents; immunotherapy, monoclonal antibodies; microenvironment

PMID:
28758974
PMCID:
PMC5578050
DOI:
10.3390/ijms18081660
[Indexed for MEDLINE]
Free PMC Article

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