Abstract
Acute myeloid leukemia (AML) is a heterogeneous disease associated with various alterations in T cell phenotype and function leading to an abnormal cell population, ultimately leading to immune exhaustion. However, restoration of T cell function allows for the execution of cytotoxic mechanisms against leukemic cells in AML patients. Therefore, long-term disease control, which requires multiple therapeutic approaches, includes those aimed at the re-establishment of cytotoxic T cell activity. AML treatments that harness the power of T lymphocytes against tumor cells have rapidly evolved over the last 3 to 5 years through various stages of preclinical and clinical development. These include tissue-infiltrated lymphocytes (TILs), bispecific antibodies, immune checkpoint inhibitors (ICIs), chimeric antigen receptor T (CAR-T) cell therapy, and tumor-specific T cell receptor gene-transduced T (TCR-T) cells. In this review, these T cell-based immunotherapies and the potential of TILs as a novel antileukemic therapy will be discussed.
Highlights
Acute myeloid leukemia (AML) is a heterogeneous disease characterized by infiltration of immature myelogenous cells in the blood, bone marrow (BM), and other tissues, which results in ineffective hematopoiesis and various symptoms of leukemic disease
With the addition of a programmed death 1 (PD-1)/PD-L1-blocking antibody, this study demonstrated AMG 330-mediated increased T cell proliferation, INF-γ secretion, and AML cell lysis
Significant progress has been made regarding understanding the complexity of the immune biology of AML in addition to noteworthy advancements in the technical development of novel T cell-based AML therapeutics
Summary
Acute myeloid leukemia (AML) is a heterogeneous disease characterized by infiltration of immature myelogenous cells in the blood, bone marrow (BM), and other tissues, which results in ineffective hematopoiesis and various symptoms of leukemic disease. Due to frequent residual disease and potential for sequential relapse, a consolidation phase often follows that may include additional chemotherapy, specific antigen-targeting therapies, myeloablative conditioning, or either autologous or allogeneic hematopoietic stem cell transplantation (HSCT) depending on the presence of certain molecular and cytogenetic abnormalities [3,4,6,7]. Donor lymphocyte infusions emphasize the role of T cells in GvL as demonstrated by their effectiveness in relapsed chronic myeloid leukemia (CML) and potential to lower relapse incidence in high-risk AML patients [12,13] Despite these advantages, significant side effects of allogeneic HSCT exist, namely, graft-versus-host disease (GvHD), which can be fatal or result in chronic health consequences. Tissue-infiltrated lymphocytes (TILs), a treatment strategy demonstrating effective tumor growth inhibition in clinical trials involving various solid malignancies, will be evaluated for their potential role in AML therapy
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