Effects of granulocyte-macrophage colony-stimulating factor and foreign helper protein as immunologic adjuvants on the T-cell response to vaccination with tyrosinase peptides
✍ Scribed by Carmen Scheibenbogen; Dirk Schadendorf; Nikolaos E. Bechrakis; Dirk Nagorsen; Udo Hofmann; Fotini Servetopoulou; Anne Letsch; Armin Philipp; Michael H. Foerster; Alexander Schmittel; Eckhard Thiel; Ulrich Keilholz
- Publisher
- John Wiley and Sons
- Year
- 2003
- Tongue
- French
- Weight
- 316 KB
- Volume
- 104
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
Abstract
Immunologic adjuvants are used to augment the immunogenicity of MHC class I–restricted peptide vaccines, but this effect has rarely been systematically evaluated in a clinical trial. We have investigated, in a phase I study, whether addition of the 2 adjuvants GM‐CSF and KLH can enhance the T‐cell response to MHC class I peptide vaccines. Forty‐three high‐risk melanoma patients who were clinically free of disease received 6 vaccinations with MHC class I–restricted tyrosinase peptides alone, with either GM‐CSF or KLH or with a combination of both adjuvants. The primary end point was induction of tyrosinase‐specific T cells, and serial T‐cell monitoring was performed in unstimulated peripheral blood samples before and after the second, fourth and sixth vaccinations by ELISPOT assay. Tyrosinase‐specific IFN‐γ‐producing T cells were detected as early as 2 weeks after the second vaccination in 5 of 9 patients vaccinated with tyrosinase peptides in combination with GM‐CSF and KLH but not in any patient vaccinated with tyrosinase peptides without adjuvants or in combination with either adjuvant alone. After 6 vaccinations, tyrosinase‐specific T cells were found in patients immunized with peptides either without adjuvants (3 of 9 patients) or in combination with the single adjuvant GM‐CSF (4 of 9 patients) but not with KLH (0 of 10 patients). Our results suggest that addition of either GM‐CSF or KLH as a single adjuvant has little impact on the immunogenicity of tyrosinase peptides. The combined application of GM‐CSF and KLH was associated with early induction of T‐cell responses. © 2003 Wiley‐Liss, Inc.