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Promiscuous survivin peptide induces robust CD4+T-cell responses in the majority of vaccinated cancer patients

  作者 Widenmeyer, M; Griesemann, H; Stevanovic, S; Feyerabend, S; Klein, R; Attig, S; Hennenlotter, J; Wernet, D; Kuprash, DV; Sazykin, AY; Pascolo, S; Stenzl, A; Gouttefangeas, C; Rammensee, HG  
  选自 期刊  International Journal of Cancer;  卷期  2012年131-1;  页码  140-149  
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[摘要]CD4+ T cells have been shown to be crucial for the induction and maintenance of cytotoxic T cell responses and to be also capable of mediating direct tumor rejection. Therefore, the anticancer therapeutic efficacy of peptide-based vaccines may be improved by addition of HLA class II epitopes to stimulate T helper cells. Survivin is an apoptosis inhibiting protein frequently overexpressed in tumors. Here we describe the first immunological evaluation of a survivin-derived CD4+ T cell epitope in a multipeptide immunotherapy trial for prostate carcinoma patients. The survivin peptide is promiscuously presented by several human HLA-DRB1 molecules and, most importantly, is naturally processed by dendritic cells. In vaccinated patients, it was able to induce frequent, robust and multifunctional CD4+ T cell responses, as monitored by IFN-? ELISPOT and intracellular cytokine staining. Thus, this HLA-DR restricted epitope is broadly immunogenic and should be valuable for stimulating T helper cells in patients suffering from a wide range of tumors.

 
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