Abstract
The cytogenetic abnormalities and molecular mutations involved in acute myeloid leukemia (AML) lead to unique treatment challenges. Although adoptive T-cell therapies (ACT) such as chimeric antigen receptor (CAR) T-cell therapy have shown promising results in the treatment of leukemias, especially B-cell malignancies, the optimal target surface antigen has yet to be discovered for AML. Alternatively, T-cell receptor (TCR)-redirected T cells can target intracellular antigens presented by HLA molecules, allowing the exploration of a broader territory of new therapeutic targets. Immunotherapy using adoptive transfer of WT1 antigen-specific TCR-T cells, for example, has had positive clinical successes in patients with AML. Nevertheless, AML can escape from immune system elimination by producing immunosuppressive factors or releasing several cytokines. This review presents recent advances of antigen-specific TCR-T cells in treating AML and discusses their challenges and future directions in clinical applications.
Highlights
Acute myeloid leukemia (AML), which is a relatively common leukemia in adult patients, results from aberrant growth in the hematopoietic system, and it has multiple clinical appearances [1, 2]
We present the state of the art and challenges of antigen-specific T-cell receptor modified-T cells (T cells) (TCR-T) cell immunotherapy for managing myeloid malignancies and discuss future directions of T-cell receptor (TCR)-T for treating AML
Adoptive transfer of antigen-specific TCR-T cells is a promising tool for AML immunotherapy due to the ability of these cells to distinguish between normal and malignant tissues
Summary
Acute myeloid leukemia (AML), which is a relatively common leukemia in adult patients, results from aberrant growth in the hematopoietic system, and it has multiple clinical appearances [1, 2]. Treatment of high-risk AML patients with adoptive transfer of Wilms’ tumor antigen 1 (WT1)-specific allogeneic TCR-T cells has shown promising results and helped prevent relapse [28]. Adoptive transfers of high-avidity TERT-specific TCR-T cells in the context of HLA-A*02:01-restricted targets have been shown potential for controlling tumor growth and prolonging the survival of tumor-bearing mice in AML [35].
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