Targeting melanoma inhibitor of apoptosis protein with cancer immunotherapy.
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.
Schmollinger
J C
JC
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.
Dranoff
G
G
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
D019496:Cancer Vaccines; D009363:Neoplasm Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor