Effects of granulocyte-macrophage colony-stimulating factor and foreign helper protein as immunologic adjuvants on the T-cell response to vaccination with tyrosinase peptides

• Verfasst von: Scheibenbogen, Carmen [VerfasserIn]
• Verfasst von: Schadendorf, Dirk [VerfasserIn]
• Titel: Effects of granulocyte-macrophage colony-stimulating factor and foreign helper protein as immunologic adjuvants on the T-cell response to vaccination with tyrosinase peptides
• Verf.angabe: 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
• E-Jahr: 2003
• Jahr: 04 February 2003
• Umfang: 7 S.
• Fussnoten: Gesehen am 18.11.2020
• Titel Quelle: Enthalten in: International journal of cancer
• Ort Quelle: Bognor Regis : Wiley-Liss, 1966
• Jahr Quelle: 2003
• Band/Heft Quelle: 104(2003), 2, Seite 188-194
• ISSN Quelle: 1097-0215
• DOI: doi:10.1002/ijc.10961
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: adjuvant
• Sach-SW: melanoma
• Sach-SW: peptide
• Sach-SW: T-cell response
• Sach-SW: tumor vaccine
• K10plus-PPN: 1739038207

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.