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Cancer Immunol Res. 2016 Jan;4(1):18-25. doi: 10.1158/2326-6066.CIR-15-0105. Epub 2015 Nov 12.

Short Peptide Vaccine Induces CD4+ T Helper Cells in Patients with Different Solid Cancers.

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Department of Dermatology, University Hospital of Erlangen, Germany.
III. Medizinische Klinik und Poliklinik, University Medical Center of the Johannes Gutenberg University, Mainz, Germany.
IOSI Oncology Institute of Southern Switzerland, Bellinzona, Switzerland.
Clinical Research Unit of the Foundation Dr. Henri Dubois-Ferrière Dinu Lipatti, Oncology Center, Hôpitaux Universitaires de Genève (HUG), Genève, Switzerland.
Onkologie/Hämatologie, Kantonsspital, St. Gallen, Switzerland.
Department of Oncology, University Hospital Zurich, Zurich, Switzerland.
Klinik und Poliklinik für Medizinische Onkologie, Inselspital, Bern, Switzerland.
Merck KGaA, Darmstadt, Germany.
Merck Serono S.A., Geneva, Geneva, Switzerland, an affiliate of Merck KGaA, Darmstadt, Germany.
Department of Dermatology, University Hospital of Erlangen, Germany.


Previous cancer vaccination trials often aimed to activate CD8(+) cytotoxic T-cell (CTL) responses with short (8-10mer) peptides and targeted CD4(+) helper T cells (TH) with HLA class II-binding longer peptides (12-16 mer) that were derived from tumor antigens. Accordingly, a study of immunomonitoring focused on the detection of CTL responses to the short, and TH responses to the long, peptides. The possible induction of concurrent TH responses to short peptides was widely neglected. In a recent phase I vaccination trial, 53 patients with different solid cancers were vaccinated with EMD640744, a cocktail of five survivin-derived short (9- or 10-mer) peptides in Montanide ISA 51VG. We monitored 49 patients and found strong CD8(+) T-cell responses in 63% of the patients. In addition, we unexpectedly found CD4(+) TH cell responses against at least two of the five short peptides in 61% (23/38) of the patients analyzed. The two peptides were recognized by HLA-DP4- and HLA-DR-restricted TH1 cells. Some short peptide-reactive (sp)CD4 T cells showed high functional avidity. Here, we show that a short peptide vaccine is able to activate a specific CD4(+) T-cell repertoire in many patients, facilitating a strong combined CD4(+)/CD8(+) T-cell response.

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