Immunotherapeutic strategies for relapse control in acute myeloid leukemia

Blood Rev. 2013 Sep;27(5):209-16. doi: 10.1016/j.blre.2013.06.006. Epub 2013 Jul 18.

Abstract

Despite that the initial phases of chemotherapy induce disappearance of leukemic cells in many patients with acute myeloid leukemia (AML), the prevention of life-threatening relapses in the post-remission phase remains a significant clinical challenge. Allogeneic bone marrow transplantation, which is available for a minority of patients, efficiently prevents recurrences of leukemia by inducing immune-mediated elimination of leukemic cells, and over the past decades, numerous immunotherapeutic protocols have been developed aiming to mimic the graft-versus-leukemia reaction for the prevention of relapse. Here we review past and present strategies for relapse control with focus on overcoming leukemia-related immunosuppression in AML. We envisage future treatment protocols, in which systemic immune activators, such as vaccines, dendritic cell-based therapies, engineered variants of IL-2, or IL-15, are combined with agents that counter immunosuppression mediated by, e.g., the PD/PDL interaction, CTLA-4, CD200, reactive oxygen species, IDO expression, CXCR4, or the KIR/class I interaction, based on characteristics of the prevailing malignant clone. This combinatorial approach may pave the way for individualized immunotherapy in AML.

Keywords: Acute myeloid leukemia; Leukemia-related immunosuppression; Maintenance therapy.

Publication types

  • Review

MeSH terms

  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / therapeutic use
  • Antineoplastic Agents / therapeutic use
  • Cancer Vaccines / therapeutic use
  • Cytokines / therapeutic use
  • Humans
  • Immunotherapy*
  • Leukemia, Myeloid, Acute / immunology*
  • Leukemia, Myeloid, Acute / pathology
  • Leukemia, Myeloid, Acute / therapy*
  • Maintenance Chemotherapy
  • Secondary Prevention*

Substances

  • Antibodies, Monoclonal
  • Antineoplastic Agents
  • Cancer Vaccines
  • Cytokines