Abstract
Simple SummaryAcute myeloid leukemia (AML) is a type of blood cancer with an extremely grim prognosis. This is due to the fact that the majority of patients will relapse after frontline treatment. Overall survival of relapsed AML is very low, and treatment options are few. T lymphocytes harnessed with antitumor T-cell receptors (TCRs) can produce objective clinical responses in certain cancers, such as melanoma, but have not entered the main road for AML. In this review, we describe the current status of the field of TCR-T-cell therapies for AML.Despite the advent of novel therapies, acute myeloid leukemia (AML) remains associated with a grim prognosis. This is exemplified by 5-year overall survival rates not exceeding 30%. Even with frontline high-intensity chemotherapy regimens and allogeneic hematopoietic stem cell transplantation, the majority of patients with AML will relapse. For these patients, treatment options are few, and novel therapies are urgently needed. Adoptive T-cell therapies represent an attractive therapeutic avenue due to the intrinsic ability of T lymphocytes to recognize tumor cells with high specificity and efficiency. In particular, T-cell therapies focused on introducing T-cell receptors (TCRs) against tumor antigens have achieved objective clinical responses in solid tumors such as synovial sarcoma and melanoma. However, contrary to chimeric antigen receptor (CAR)-T cells with groundbreaking results in B-cell malignancies, the use of TCR-T cells for hematological malignancies is still in its infancy. In this review, we provide an overview of the status and clinical advances in adoptive TCR-T-cell therapy for the treatment of AML.
Highlights
Acute myeloid leukemia (AML) is a type of blood cancer that carries a grim prognosis, despite considerable therapeutic advances in the last decade
Two of these three completed clinical trials used escalating doses of human leukocyte antigen (HLA)-A*02:01-restricted Wilms’ tumor 1 (WT1)-specific T-cell receptor (TCR)-T cells [51,52,53]
In NCT01621724, WT1-specific T cells persisted one year after infusion in four out of a total of seven patients with AML and chronic myeloid leukemia (CML) [51]
Summary
Acute myeloid leukemia (AML) is a type of blood cancer that carries a grim prognosis, despite considerable therapeutic advances in the last decade. Allo-HSCT, which is considered an immunotherapeutic strategy, since part of its mode of action involves the administration of T-lymphocytes that can recognize and eliminate the leukemic cells, is the gold standard post-remission treatment in AML. As discussed above, it is generally reserved for younger patients. Even with allo-HSCT, the majority of AML patients will relapse, explaining the poor 5-year overall survival rate of only 30% [2].
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