Immune therapies in acute myeloid leukemia: a focus on monoclonal antibodies and immune checkpoint inhibitors

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Abstract

Purpose of review

This review discusses the rationale, efficacy, and toxicity of a variety of immune approaches being evaluated in the therapy of acute myeloid leukemia (AML) including naked and conjugated monoclonal antibodies, bispecific T-cell engager antibodies, and immune checkpoint blockade via antibodies targeting cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed-death 1 (PD-1).

Recent findings

The stellar success of immune therapies that harness the power of T cells in solid tumors and an improved understanding of the immune system in patients with hematologic malignancies have resulted in major efforts to develop immune therapies for the treatment of patients with AML. Monoclonal antibodies in AML therapy include naked antibodies against AML surface antigens such as CD33 (e.g. lintuzumab) or CD38 (e.g. daratumumab), antibodies conjugated to toxins in various anti-CD33 (gemtuzumab ozogamicin, SGN33A, IMGN779) and anti-CD123 (SL-401, SGN-CD123A) formulations, and antibodies conjugated to radioactive particles such as 131I or 225Ac-labeled anti-CD33 or anti-CD45 antibodies. Additional antigenic targets of interest in AML include CLL1, CD38, CD25, TIM3, FLT3, and others. Approaches to harness the body's own T cells against AML include antibodies that recruit and induce cytotoxicity of tumor cells by T cells (bispecific T-cell engager [BiTE] such as CD33 x CD3 (e.g. AMG 330) or CD123 x CD3 (e.g. flotetuzumab, JNJ-63709178) or antibodies that block immune checkpoint receptors CTLA4 (e.g. ipilimumab) or PD1/PD-L1 (e.g. nivolumab, pembrolizumab, avelumab) on T cells, unleashing the patients’ T cells against leukemic cells.

Summary

The ongoing trials and well designed correlative interrogation of the immune system in patients treated on such trials will further enhance our understanding and clinical application of immune therapies as single-agent and combination approaches for the treatment of AML.

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