Effects of granulocyte-macrophage colony-stimulating factor and foreign helper protein as immunologic adjuvants on the T-cell response to vaccination with tyrosinase peptides
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 r...
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| Main Authors: | , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
04 February 2003
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| In: |
International journal of cancer
Year: 2003, Volume: 104, Issue: 2, Pages: 188-194 |
| ISSN: | 1097-0215 |
| DOI: | https://doi.org/10.1002/ijc.10961 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/https://doi.org/10.1002/ijc.10961 Verlag, lizenzpflichtig, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1002/ijc.10961 
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| Author Notes: | Carmen Scheibenbogen, Dirk Schadendorf, Nikolaos E. Bechrakis, Dirk Nagorsen, Udo Hofmann, Fotini Servetopoulou, Anne Letsch, Armin Philipp, Michael H. Foerster, Alexander Schmittel, Eckhard Thiel and Ulrich Keilholz |
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| 520 | |a 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. | ||
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