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

Gross, Stefanie; Lennerz, Volker; Gallerani, Elisa; Mach, Nicolas; Böhm, Steffen; Hess, Dagmar; von Boehmer, Lotta; Knuth, Alexander; Ochsenbein, Adrian; Gnad-Vogt, Ulrike; Forssmann, Ulf; Woelfel, Thomas; Kaempgen, Eckhart (2016). Short Peptide Vaccine Induces CD4+ T Helper Cells in Patients with Different Solid Cancers. Cancer immunology research, 4(1), pp. 18-25. American Association for Cancer Research 10.1158/2326-6066.CIR-15-0105

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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. Cancer Immunol Res; 4(1); 18-25. ©2015 AACR.

Item Type:	Journal Article (Original Article)
Division/Institute:	04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Medical Oncology
UniBE Contributor:	Ochsenbein, Adrian
Subjects:	600 Technology > 610 Medicine & health
ISSN:	2326-6074
Publisher:	American Association for Cancer Research
Language:	English
Submitter:	Marianne Zahn
Date Deposited:	26 Jul 2016 15:18
Last Modified:	05 Dec 2022 14:52
Publisher DOI:	10.1158/2326-6066.CIR-15-0105
PubMed ID:	26563311
URI:	https://boris.unibe.ch/id/eprint/77228