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Published on: February 17, 2022
CAR-T Cells in Acute Myeloid Leukemia: Where Do We Stand?
Daniela Damiani1,2, Mario Tiribelli1,2
1Division of Hematology and Stem Cell Transplantation, University Hospital, 33100 Udine, Italy.
Abstract:
Despite recent advances, the prognosis of acute myeloid leukemia (AML) remains unsatisfactory due to disease recurrence and the development of resistance to both conventional and novel therapies. Engineered T cells expressing chimeric antigen receptors (CARs) on their cellular surface represent one of the most promising anticancer agents. CAR-T cells are increasingly used in patients with B cell malignancies, with remarkable clinical results despite some immune-related toxicities. However, at present, the role of CAR-T cells in myeloid neoplasms, including AML, is extremely limited, as specific molecular targets for immune cells are generally lacking on AML blasts. Besides the paucity of dispensable targets, as myeloid antigens are often co-expressed on normal hematopoietic stem and progenitor cells with potentially intolerable myeloablation, the AML microenvironment is hostile to T cell proliferation due to inhibitory soluble factors. In addition, the rapidly progressive nature of the disease further complicates the use of CAR-T in AML. This review discusses the current state of CAR-T cell therapy in AML, including the still scanty clinical evidence and the potential approaches to overcome its limitations, including genetic modifications and combinatorial strategies, to make CAR-T cell therapy an effective option for AML patients.
Insights
Chimeric antigen receptor T-cell (CAR-T) therapy shows promise for acute myeloid leukemia (AML), but faces challenges like target scarcity and a hostile tumor microenvironment. Research is exploring genetic modifications and combination strategies to improve CAR-T efficacy in AML treatment.
Area of Science:
- Oncology
- Immunotherapy
- Hematology
Background:
- Acute myeloid leukemia (AML) prognosis remains poor due to treatment resistance and recurrence.
- Chimeric antigen receptor T-cell (CAR-T) therapy has shown success in B cell malignancies but is underutilized in AML.
- Significant hurdles exist for CAR-T therapy in AML, including lack of specific targets and an immunosuppressive tumor microenvironment.
Purpose of the Study:
- To review the current status of CAR-T cell therapy in AML.
- To identify and discuss the limitations hindering CAR-T efficacy in AML.
- To explore potential strategies for overcoming these limitations and advancing CAR-T therapy for AML patients.
Main Methods:
- Literature review of current CAR-T cell therapy applications in AML.
- Analysis of challenges including target identification, antigen co-expression, and the AML microenvironment.
- Discussion of innovative approaches such as genetic engineering and combinatorial treatments.
Main Results:
- Limited clinical evidence currently exists for CAR-T therapy in AML.
- Key challenges include the scarcity of AML-specific targets and antigen co-expression on essential stem cells.
- The AML microenvironment contains soluble factors that inhibit T-cell function.
Conclusions:
- CAR-T cell therapy holds potential for AML but requires overcoming significant biological and technical barriers.
- Genetic modifications and combination strategies are crucial for enhancing CAR-T efficacy.
- Further research and development are needed to establish CAR-T as a viable treatment option for AML.

