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HLA-A24 and survivin: possibilities in therapeutic vaccination against cancer
Authors:Mads Hald Andersen  Rikke B Soerensen  Jürgen C Becker  Per thor Straten
Institution:1. Center for Cancer Immunotherapy (CCIT), Department of Hematology, Herlev University Hospital, 2730, Herlev, Dk, Denmark
2. Department of Dermatology, University of Würzburg, D-97080, Würzburg, Germany
Abstract:Recently, it was described that an HLA-A24 restricted peptide derived from the survivin splice variant survivin-2B can be recognized by CD8(+) cytotoxic T-cells. The identification of an HLA-A24 epitope is critical for survivin-based immunotherapy as HLA-24 is the most frequent HLA allele in Asia. Consequently, this survivin-2B epitope is already a target in a clinical study in patients with advanced or recurrent colorectal cancer expressing survivin. However, the splice variant survivin-2B has been described to be pro-apoptotic, and is only expressed at low levels in most malignant tissues. Furthermore, survivin-2B expression are significantly decreased in later tumor stages and inversely correlated with tumor differentiation and invasion. Consequently, survivin is a more general vaccination candidate than the splice variant survivin-2B. Here, we on the basis of spontaneous immune responses in HLA-A24+ cancer patients describes that a HLA-A24-restricted survivin epitopes does indeed exist. Consequently, this epitope is an attractive target for the ongoing survivin-based peptide immunotherapy against cancer.
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