title: Promiscuous survivin peptide induces robust CD4+ T-cell responses in the majority of vaccinated cancer patients.
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.
authors.affiliation: Department of Immunology, Institute for Cell Biology, Eberhard Karls University, Tübingen 72076, Germany.
authors.forename: Melanie
authors.initials: M
authors.lastname: Widenmeyer
authors.forename: Heinrich
authors.initials: H
authors.lastname: Griesemann
authors.forename: Stefan
authors.initials: S
authors.lastname: Stevanović
authors.forename: Susan
authors.initials: S
authors.lastname: Feyerabend
authors.forename: Reinhild
authors.initials: R
authors.lastname: Klein
authors.forename: Sebastian
authors.initials: S
authors.lastname: Attig
authors.forename: Jörg
authors.initials: J
authors.lastname: Hennenlotter
authors.forename: Dorothee
authors.initials: D
authors.lastname: Wernet
authors.forename: Dmitri V
authors.initials: DV
authors.lastname: Kuprash
authors.forename: Alexei Y
authors.initials: AY
authors.lastname: Sazykin
authors.forename: Steve
authors.initials: S
authors.lastname: Pascolo
authors.forename: Arnulf
authors.initials: A
authors.lastname: Stenzl
authors.forename: Cécile
authors.initials: C
authors.lastname: Gouttefangeas
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: Rammensee
mesh_terms: D000368:Aged; D000951:Antigens, Neoplasm / Q000276:immunology; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000276:immunology* / Q000627:therapeutic use; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D059811:HLA-DRB1 Chains / Q000276:immunology; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000276:immunology; D011471:Prostatic Neoplasms / Q000276:immunology* / Q000628:therapy*; D000077022:Survivin; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism
chemical_list: D000951:Antigens, Neoplasm; C107489:BIRC5 protein, human; D019496:Cancer Vaccines; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D059811:HLA-DRB1 Chains; D051034:Inhibitor of Apoptosis Proteins; D010446:Peptide Fragments; D000077022:Survivin; D007371:Interferon-gamma