Immunotherapy for Acute Myeloid Leukemia: Current Trends, Challenges, and Strategies

Abstract

<b><i>Background:</i></b> In the past decade, there have been significant breakthroughs in immunotherapies for B-cell lymphoid malignancies and multiple myeloma, but progress has been much less for acute myeloid leukemia (AML). Nevertheless, challenge begets innovation and several therapeutic strategies are under investigation. <b><i>Summary:</i></b> In this review, we review the state of the art in AML immunotherapy including CD33- and CD123-targeted agents, immune checkpoint inhibition, and adoptive cell therapy strategies. We also share conceptual frameworks for approaching the growing catalog of investigational AML immunotherapies and propose future directions for the field. <b><i>Key Messages:</i></b> Immunotherapies for AML face significant challenges but novel strategies are in development.

Monocytic Differentiation in Acute Myeloid Leukemia Cells: Diagnostic Criteria, Biological Heterogeneity, Mitochondrial Metabolism, Resistance to and Induction by Targeted Therapies

“…Finally, FAB-M4/M5 AML cells show a high expression of several chemokines involved in local T-cell chemotaxis [ 49 , 50 ]. Although effector T cells can mediate antileukemic effects (even though escape mechanisms may also exist) [ 66 , 67 , 68 ], activated T cells can also release cytokines that mediate direct (i.e., antiapoptotic hematopoietic growth factors), as well as indirect (e.g., recruitment/differentiation of M2-like macrophages), AML-supporting effects [ 69 ]. However, to the best of our knowledge, no previous studies have investigated whether the extracellular stroma or the composition/education of nonleukemic bone marrow cells differ between FAB-M4/M5 patients and other AML patients.…”

Broadening the horizon: potential applications of CAR-T cells beyond current indications

“…To achieve these goals, researchers are employing multiple methods. These include suicide switches (anti-CD20 agents against CAR-T cells carrying CD20), logic gating (typically AND, NOT, and OR) to improve target recognition, and the genetic engineering of hematopoietic stem cells (HSCs) to reduce target antigen expression on their surface ( 171 ). Specific logic gating strategies have been proposed for anti-CD93 CAR-T cells ( 172 ) and an IF-BETTER gate for the targeting of ADGRE2 and CLEC12A ( 173 ).…”