Targeting melanoma inhibitor of apoptosis protein with cancer immunotherapy

Apoptosis. 2004 May;9(3):309-13. doi: 10.1023/b:appt.0000025807.59668.5e.


Aberrantly expressed or mutated proteins in cancer cells evoke immune recognition, but host reactions are usually insufficient to prevent disease progression. Vaccination with irradiated tumor cells engineered to secrete granulocyte-macrophage colony stimulating factor (GM-CSF) augments host immunity through improved tumor antigen presentation by recruited dendritic cells and macrophages. By analyzing the immune response of a metastatic melanoma patient who achieved a long-term response to vaccination, we identified melanoma inhibitor of apoptosis protein (ML-IAP) as a target for immune-mediated tumor destruction. Vaccination stimulated a coordinated cellular and humoral reaction to ML-IAP that was associated with extensive tumor necrosis, whereas lethal disease progression was linked with the loss of ML-IAP expression and the absence of intra-tumoral lymphocyte infiltrates. These findings demonstrate that ML-IAP can serve as a tumor rejection antigen, although additional vaccine targets will be required to circumvent immune escape and tumor heterogeneity.

Publication types

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

MeSH terms

  • Apoptosis / immunology*
  • Cancer Vaccines / immunology
  • Cancer Vaccines / therapeutic use
  • Chromosomes, Human, Pair 20
  • Follow-Up Studies
  • Gene Targeting*
  • Genetic Engineering
  • Granulocyte-Macrophage Colony-Stimulating Factor / therapeutic use
  • Humans
  • Immunotherapy
  • Melanoma / immunology*
  • Melanoma / pathology
  • Melanoma / therapy*
  • Neoplasm Proteins / immunology*
  • Survival Analysis


  • Cancer Vaccines
  • Neoplasm Proteins
  • Granulocyte-Macrophage Colony-Stimulating Factor