Immune-Based Therapeutic Strategies for Acute Myeloid Leukemia

Abstract

The development and design of immune-based strategies have become an increasingly important topic during the last few years in acute myeloid leukemia (AML), based on successful immunotherapies in solid cancer. The spectrum ranges from antibody drug conjugates, immune checkpoint inhibitors blocking programmed cell death protein 1 (PD1), cytotoxic T lymphocyte antigen 4 (CTLA4) or T cell immunoglobulin and mucin domain containing-3 (TIM3), to T-cell based monoclonal and bispecific T-cell engager antibodies, chimeric antigen receptor-T-cell (CAR-T) approaches and leukemia vaccines. Currently, there are many substances in development and multiple phase I/II studies are ongoing. These trials will help us to deepen our understanding of the pathogenesis of AML and facilitate the best immunotherapeutic strategy in AML. We discuss here the mode of action of immune-based therapies and provide an overview of the available data.

Antineoplastic activity of biogenic silver and gold nanoparticles to combat leukemia: Beginning a new era in cancer theragnostic

“…In this case, the same as other types of cancer, different methods can be used, including conjugation of anti-body to drugs, inhibition of the programmed cell death protein 1 (PD1), T cell immunoglobulin, and cytotoxic T lymphocyte antigen 4 (CTLA4), via immune checkpoint blockers, and finally vaccines. However, these therapeutic methods are in their early stages, and several studies are needed to reach the decisive results [ 23 , 24 ].…”

The Association between Immune Checkpoint Proteins and Therapy Outcomes in Acute Myeloid Leukaemia Patients

“…Interestingly, lack of PD-1 in the knock-out AML mouse model led to improved survival of the animals, thus indicating a crucial contribution of that protein in the disease pathogenesis [ 10 ]. Noteworthily, the PD-1/PD-L1 axis is just one of numerous immune checkpoints currently being tested as potential targets for novel immunotherapies of AML [ 3 ].…”

“…That field constitutes one of the most promising directions also in the context of AML management, apart from CAR T cells, bispecific T cell engaging antibodies (BiTEs) or dendritic cell vaccines. The need for novel drugs is predominantly associated with a still high number of patients with poor prognosis to standard therapy [ 2 , 3 ].…”

Preclinical Characterization of the Anti-Leukemia Activity of the CD33/CD16a/NKG2D Immune-Modulating TriNKET® CC-96191

“…The success of T cell-engaging bispecific antibodies (BsAbs) in lymphoid malignancies has raised enthusiasm for similar therapeutics in AML-targeting CD33. Several CD33/CD3 BsAbs have entered clinical testing, with initial results indicating some efficacy [ 17 , 18 , 19 , 20 , 21 ]. However, toxicities from activated T cells cause significant challenges for their use, providing a strong rationale to explore drugs engaging other immune cells such as natural killer (NK) cells that might elicit potent anti-AML activity more safely due to their production of reduced levels of cytokines compared with T cells and their ability to discriminate healthy and malignant cells [ 22 , 23 , 24 , 25 , 26 ].…”