Int J Cancer. 2011 Aug 19. doi: 10.1002/ijc.26365. [Epub ahead of print]

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

Widenmeyer M, Griesemann H, Stevanović S, Feyerabend S, Klein R, Attig S, Hennenlotter J, Wernet D, Kuprash DV, Sazykin AY, Pascolo S, Stenzl A, Gouttefangeas C, Rammensee HG.

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Department of Immunology, Institute for Cell Biology, Eberhard Karls University, Tübingen 72076, Germany.

Abstract

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-γ 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.

PMID:: 21858810; [PubMed - as supplied by publisher]

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

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