title: Targeting melanoma inhibitor of apoptosis protein with cancer immunotherapy.
abstract: 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.
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute and Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
authors.forename: J C
authors.initials: JC
authors.lastname: Schmollinger
authors.forename: G
authors.initials: G
authors.lastname: Dranoff
mesh_terms: D017209:Apoptosis / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use; D002890:Chromosomes, Human, Pair 20; D005500:Follow-Up Studies; D018390:Gene Targeting; D005818:Genetic Engineering; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use; D006801:Humans; D007167:Immunotherapy; D008545:Melanoma / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D009363:Neoplasm Proteins / Q000276:immunology*; D016019:Survival Analysis
chemical_list: D019496:Cancer Vaccines; D009363:Neoplasm Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor