Immunomodulatory drugs: Immune checkpoint agents in acute leukemia

Hanna A. Knaus, Christopher G. Kanakry, Leo Luznik, Ivana Gojo

Research output: Contribution to journalReview article

Abstract

Intrinsic immune responses to acute leukemia are inhibited by a variety of mechanisms, such as aberrant antigen expression by leukemia cells, secretion of immunosuppressive cytokines and expression of inhibitory enzymes in the tumor microenvironment, expansion of immunoregulatory cells, and activation of immune checkpoint pathways, all leading to T cell dysfunction and/or exhaustion. Leukemic cells, similar to other tumor cells, hijack these inhibitory pathways to evade immune recognition and destruction by cytotoxic T lymphocytes. Thus, blockade of immune checkpoints has emerged as a highly promising approach to augment innate anti-tumor immunity in order to treat malignancies. Most evidence for the clinical efficacy of this immunotherapeutic strategy has been seen in patients with metastatic melanoma, where anti-CTLA-4 and anti-PD-1 antibodies have recently revolutionized treatment of this lethal disease with otherwise limited treatment options. To meet the high demand for new treatment strategies in acute leukemia, clinical testing of these promising therapies is commencing. Herein, we review the biology of multiple inhibitory checkpoints (including CTLA-4, PD-1, TIM-3, LAG-3, BTLA, and CD200R) and their contribution to immune evasion by acute leukemias. In addition, we discuss the current state of preclinical and clinical studies of immune checkpoint inhibition in acute leukemia, which seek to harness the body’s own immune system to fight leukemic cells.

Original languageEnglish (US)
Pages (from-to)315-331
Number of pages17
JournalCurrent Drug Targets
Volume18
Issue number3
DOIs
StatePublished - Mar 1 2017

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Contraception Behavior
Leukemia
T-cells
Neoplasms
Inborn Errors Amino Acid Metabolism
Cape Verde
Saimiriine herpesvirus 2
Supravalvular Aortic Stenosis
Blood Stains
Immune system
Castration
Autistic Disorder
Immune Evasion
Tumor Microenvironment
Cytotoxic T-Lymphocytes
Immunosuppressive Agents
Immune System
Immunity
Melanoma
Cytokines

Keywords

  • Acute lymphoblastic leukemia
  • Acute myeloid leukemia
  • Co-inhibitory receptor
  • Immune checkpoint pathway
  • Immune evasion
  • Immunotherapy
  • Monoclonal antibody
  • T cells

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology
  • Drug Discovery
  • Clinical Biochemistry

Cite this

Immunomodulatory drugs : Immune checkpoint agents in acute leukemia. / Knaus, Hanna A.; Kanakry, Christopher G.; Luznik, Leo; Gojo, Ivana.

In: Current Drug Targets, Vol. 18, No. 3, 01.03.2017, p. 315-331.

Research output: Contribution to journalReview article

Knaus, Hanna A.; Kanakry, Christopher G.; Luznik, Leo; Gojo, Ivana / Immunomodulatory drugs : Immune checkpoint agents in acute leukemia.

In: Current Drug Targets, Vol. 18, No. 3, 01.03.2017, p. 315-331.

Research output: Contribution to journalReview article

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