Natural killer cell-based immunotherapy for acute myeloid leukemia
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REVIEW
Natural killer cell‑based immunotherapy for acute myeloid leukemia Jing Xu and Ting Niu*
Abstract Despite considerable progress has been achieved in the treatment of acute myeloid leukemia over the past decades, relapse remains a major problem. Novel therapeutic options aimed at attaining minimal residual disease-negative complete remission are expected to reduce the incidence of relapse and prolong survival. Natural killer cell-based immunotherapy is put forward as an option to tackle the unmet clinical needs. There have been an increasing number of therapeutic dimensions ranging from adoptive NK cell transfer, chimeric antigen receptor-modified NK cells, antibodies, cytokines to immunomodulatory drugs. In this review, we will summarize different forms of NK cell-based immunotherapy for AML based on preclinical investigations and clinical trials. Keywords: Acute myeloid leukemia, Natural killer cells, Immunotherapy, Adoptive NK cell transfer, Chimeric antigen receptor-modified NK cells, Antibodies, Cytokines Background Acute myeloid leukemia (AML) is a clinically and genetically heterogeneous disease with unsatisfactory outcomes. Over the last few years, considerable progress has been achieved in the treatment of AML with the development and implementation of new drugs [1, 2]. However, allogeneic hematopoietic cell transplantation (HCT) has been recognized as the only way to cure AML so far and relapse remains a major problem. Novel therapeutic options aimed at attaining minimal residual disease (MRD)-negative complete remission (CR) are expected to reduce the incidence of relapse and prolong survival. Thus, immunotherapy becomes an option to tackle unmet clinical needs in AML [3, 4]. Immunotherapy has been recognized as an incredibly promising therapeutic strategy for numerous cancers [5]. The adoption of this treatment modality is based on mechanisms of immune surveillance/response and cancer escape [6]. Under physiological conditions, immune
*Correspondence: [email protected] Department of Hematology, West China Hospital, Sichuan University, Chengdu 610041, China
cells and substances in the immune system play pivotal roles in detecting and destroying pathogen-infected or neoplastically transformed cells. But they become less potent in cancer elimination when malignant cells display the loss of antigenicity and/or immunogenicity and are surrounded by an immunosuppressive microenvironment [6]. Thus, immunotherapy with strategies of reboosting patients’ own immune system or initiating new immune response to fight cancers has been demonstrated with the capacity of producing sustainable clinical benefits against both solid and hematological malignancies [7–9]. Natural killer (NK) cell-based immunotherapy represents one of the novel immunotherapeutic strategies recently, unleashing immune suppression of NK cells to attack various cancers [10–12]. With the progressive elucidation of NK cell immunobiology and the development of manipulative techniques, the field of NK cellbased immunotherapy in h
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