Previous cancer vaccination trials often aimed at the activation of CD8+ cytotoxic T cell (CTL) responses using short (8-10mer) peptides and targeted CD4+ helper T cells (TH) with HLA class II-binding longer peptides (12-16mers) derived from tumor antigens. Accordingly, immunomonitoring of these studies focused on the detection of CTL responses against short and TH-responses to the long peptides applied. A 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 10mer) peptides in Montanide® ISA 51VG. Performing thorough immunomonitoring in 49 patients, we detected strong CD8+ T cell responses in 63 % of the patients. In addition, we found, yet unexpected, CD4+ TH cell responses against at least two of the five short peptides in 61% (23/38) of 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.
- Received April 16, 2015.
- Revision received August 12, 2015.
- Accepted September 4, 2015.
- Copyright © 2015, American Association for Cancer Research.