Antigen-specific immunotherapy for acute myeloid leukemia: where are we now, and where do we go from here?

Expert Rev Hematol. 2016;9(4):335-50. doi: 10.1586/17474086.2016.1142868. Epub 2016 Feb 6.

Abstract

Antigen-specific immunotherapies have long been pursued as a means to improve the outcomes of patients with acute myeloid leukemia (AML). Success thus far has been limited, and many therapeutics have either been ineffective in the clinic or have an uncertain impact on patient outcomes. Only the CD33 antibody-drug conjugate gemtuzumab ozogamicin provided benefit in randomized studies. Here, we briefly review where we currently are with antigen-specific AML immunotherapy and where we might go from here. Besides the exploration of novel target antigens, ongoing preclinical and clinical efforts aim to improve existing immunotherapy modalities and focus on developing novel therapeutics such as bispecific antibodies and gene-modified immune effector cells. Ultimately, clinical studies need to address the question of ideal target(s) in AML, a disease of great antigenic diversity, and clarify how the upcoming immunotherapeutics should be best used and what level of supportive care is required for their safe administration.

Keywords: Acute myeloid leukemia; adoptive immunotherapy; antibody; antibody-drug conjugate; bispecific antibody; chimeric antigen receptor; gemtuzumab ozogamicin; immunotoxin; radioimmunotherapy; vaccine.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Aminoglycosides / chemistry
  • Aminoglycosides / therapeutic use
  • Antibodies, Bispecific / chemistry
  • Antibodies, Bispecific / therapeutic use
  • Antibodies, Monoclonal / chemistry
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Humanized / chemistry
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Antigens / immunology*
  • Gemtuzumab
  • Humans
  • Immunoconjugates / therapeutic use
  • Immunotherapy
  • Immunotoxins / chemistry
  • Immunotoxins / therapeutic use
  • Leukemia, Myeloid, Acute / therapy*
  • Peptides / chemistry
  • Peptides / therapeutic use
  • Radiopharmaceuticals / chemistry
  • Radiopharmaceuticals / therapeutic use
  • Sialic Acid Binding Ig-like Lectin 3 / immunology

Substances

  • Aminoglycosides
  • Antibodies, Bispecific
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antigens
  • CD33 protein, human
  • Immunoconjugates
  • Immunotoxins
  • Peptides
  • Radiopharmaceuticals
  • Sialic Acid Binding Ig-like Lectin 3
  • Gemtuzumab