T-cell-based immunotherapy of acute myeloid leukemia: current concepts and future developments

• Published in: Leukemia Vol. 35; no. 7; pp. 1843 - 1863
• Main Authors: Daver, Naval, Alotaibi, Ahmad S, Bücklein, Veit, Subklewe, Marion
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01.07.2021; Nature Publishing Group UK
• Subjects: Acute myeloid leukemia; Animals; Antibodies; Antigens; CD123 antigen; Cellular therapy; Chimeric antigen receptors; Chronic lymphocytic leukemia; CTLA-4 protein; Disease control; Forecasts and trends; Health aspects; Health services; Humans; Immune checkpoint inhibitors; Immune Checkpoint Inhibitors - immunology; Immune system; Immunotherapy; Immunotherapy - methods; Leukemia; Leukemia research; Leukemia, Myeloid, Acute - immunology; Leukemia, Myeloid, Acute - therapy; Lymphocytes; Lymphocytes T; Methods; Myeloid leukemia; Patients; PD-1 protein; PD-L1 protein; Receptors; Receptors, Chimeric Antigen - immunology; Review; Solid tumors; Stellar evolution; T cells; T-Lymphocytes - immunology; Tumors; United States
• ISSN: 0887-6924; 1476-5551; 1476-5551
• DOI: 10.1038/s41375-021-01253-x

Acute myeloid leukemia (AML) is a heterogeneous disease linked to a broad spectrum of molecular alterations, and as such, long-term disease control requires multiple therapeutic approaches. Driven largely by an improved understanding and targeting of these molecular aberrations, AML treatment has rapidly evolved over the last 3-5 years. The stellar successes of immunotherapies that harness the power of T cells to treat solid tumors and an improved understanding of the immune systems of patients with hematologic malignancies have led to major efforts to develop immunotherapies for the treatment of patients with AML. Several immunotherapies that harness T cells against AML are in various stages of preclinical and clinical development. These include bispecific and dual antigen receptor-targeting antibodies (targeted to CD33, CD123, CLL-1, and others), chimeric antigen receptor (CAR) T-cell therapies, and T-cell immune checkpoint inhibitors (including those targeting PD-1, PD-L1, CTLA-4, and newer targets such as TIM3 and STING). The current and future directions of these T-cell-based immunotherapies in the treatment landscape of AML are discussed in this review.