Cited by 70Immunotherapy and Immune Responsesvaccines and immunoinformatics approachesCancer Immunotherapy and Biomarkers

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

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Widenmeyer, Melanie, Griesemann, Heinrich, Stevanović, Stefan, Feyerabend, Susan, Klein, Reinhild, Attig, Sebastian, Hennenlotter, Jörg, Wernet, Dorothee +6 more·2012·International Journal of Cancer

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.

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Crossref · 10.1002/ijc.26365

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  • In an HLA-A*02:01+ patient population, epitopes of the expressed TAAs will also be presented on the tumours of most patients to the immune system, because CVGBM encodes HLA-A*02:01-restricted epitopes for three of the TAAs and a pan-DR-restricted epitope for the fourth TAA (Survivin), which is presented by many HLA class II molecules.

    “Importantly, in an HLA-A*02:01+ patient population, epitopes of the expressed TAAs will also be presented on the tumours of most patients to the immune system, as CVGBM encodes HLA-A*02:01-restricted epitopes for three of the TAAs (BCAN, NLGN4X, PTPRZ1) and a pan-DR-restricted epitope for the fourth TAA (Survivin), which is presented by many HLA class II molecules [29].”

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Authors
Widenmeyer, M., Griesemann, H., Stevanović, S., Feyerabend, S., Klein, R., Attig, S., Hennenlotter, J., Wernet, D., Kuprash, D. V., Sazykin, A. Y., Pascolo, S., Stenzl, A., Gouttefangeas, C., & Rammensee, H.
Affiliations
  • University of Tübingen (DE)
  • Universitätsklinikum Tübingen (DE)
Corresponding author
Gouttefangeas, Cécile
Venue
International Journal of Cancer
Publisher
Wiley
Published
2011-09-14
Volume
131
Issue
1
Pages
140-149
ISSN
  • 0020-7136 (ISSN-L)
  • 1097-0215
OpenAlex
W2094294085
Cited by
70
References
50
Citations by year
2025: 4 · 2023: 5 · 2022: 4 · 2021: 6 · 2020: 4 · 2019: 4 · 2018: 8 · 2017: 4 · 2016: 7 · 2015: 6 · 2014: 9 · 2013: 7 · 2012: 1
FWCI
2.39
Type
journal article
Language
en
Open access
Locations
  • International Journal of Cancer (publishedVersion)
  • PubMed (publishedVersion)
  • Zurich Open Repository and Archive (University of Zurich) (submittedVersion)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
  • Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
Keywords
survivin, CD4+ T cell epitopes, HLA-DRB1, HLA class II epitopes, peptide-based cancer vaccines, prostate cancer, interferon-gamma, cancer immunotherapy, apoptosis inhibitor
MeSH terms
Survivin, Aged, Antigens, Neoplasm, Dendritic Cells, T-Lymphocytes, Helper-Inducer, Humans, Interferon-gamma, Lymphocyte Activation, Male, Middle Aged, Peptide Fragments, Prostatic Neoplasms, T-Lymphocytes, Cytotoxic, Cytokines, Epitopes, T-Lymphocyte, Cancer Vaccines, Inhibitor of Apoptosis Proteins, HLA-DRB1 Chains

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