Chimeric antigen receptor T cell therapies for acute myeloid leukemia
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REVIEW
Chimeric antigen receptor T cell therapies for acute myeloid leukemia Bin Gu, Jianhong Chu, Depei Wu (
✉)
Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Collaborative Innovation Center of Hematology of Soochow University, Suzhou Institute of Blood and Marrow Transplantation, Suzhou 215006, China
© The Author(s) 2020. This article is published with open access at link.springer.com and journal.hep.com.cn 2020
Abstract Chimeric antigen receptor T cell (CAR T) therapies have achieved unprecedented efficacy in B-cell tumors, prompting scientists and doctors to exploit this strategy to treat other tumor types. Acute myeloid leukemia (AML) is a group of heterogeneous myeloid malignancies. Relapse remains the main cause of treatment failure, especially for patients with intermediate or high risk stratification. Allogeneic hematopoietic stem cell transplantation could be an effective therapy because of the graft-versus-leukemia effect, which unfortunately puts the patient at risk of serious complications, such as graft-versus-host disease. Although the identification of an ideal target antigen for AML is challenging, CAR T therapy remains a highly promising strategy for AML patients, particularly for those who are ineligible to receive a transplantation or have positive minimal residual disease. In this review, we focus on the most recent and promising advances in CAR T therapies for AML. Keywords
acute myeloid leukemia; CAR T; immunotherapy
Introduction Acute myeloid leukemia (AML) is the most common type of leukemia showing heterogeneity behavior and is characterized by the clonal expansion of myeloid blasts. Despite recent improvements in treatment, the complete remission (CR) rates for AML are approximately 70% in younger adults and only 40%–60% in older patients (more than 60 years old) [1,2]. Disease recurrence remains the most common cause of treatment failure, and the 5-year survival of AML patients with intermediate and high risk cytogenetics was no more than 41% [3–5]. Allogeneic hematopoietic stem cell transplantation (Allo-HSCT) could be an effective therapy for AML patients through the graft-versus-leukemia effect mediated by donor T lymphocytes. However, it is often accompanied with the risk of life-threatening graft-versus-host disease [6]. The physiological mechanism responsible for the killing effect of cytotoxic T lymphocytes has been well studied. A recognition signal from T cell receptors (TCRs) is the first step; this is complemented by a costimulatory signal to further augment the activation of cytotoxic T Received August 5, 2019; accepted February 16, 2020 Correspondence: Depei Wu, [email protected]
lymphocytes (Fig. 1). A TCR could recognize an antigen in the context of major histocompatibility complex (MHC) presentation. In stark contrast, chimeric antigen receptor (CAR) is an MHC-independent model that is commonly composed of an extracellular domain with a single-chain variable fragment (scFv) from a monoclonal antibody, a hinge region, a transmemb
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