Targeting melanoma inhibitor of apoptosis protein with cancer immunotherapy |
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Authors: | J. C. Schmollinger G. Dranoff |
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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. |
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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. |
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Keywords: | cancer vaccine granulocyte-macrophage colony stimulating factor inhibitor of apoptosis protein melanoma |
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