title: Effects of granulocyte-macrophage colony-stimulating factor and foreign helper protein as immunologic adjuvants on the T-cell response to vaccination with tyrosinase peptides.
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-gamma-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.
authors.affiliation: Medizinische Klinik III, Haematologie, Onkologie und Transfusionsmedizin, Universitätsklinikum Benjamin-Franklin, Freie Universität Berlin, Berlin, Germany.
authors.forename: Carmen
authors.initials: C
authors.lastname: Scheibenbogen
authors.forename: Dirk
authors.initials: D
authors.lastname: Schadendorf
authors.forename: Nikolaos E
authors.initials: NE
authors.lastname: Bechrakis
authors.forename: Dirk
authors.initials: D
authors.lastname: Nagorsen
authors.forename: Udo
authors.initials: U
authors.lastname: Hofmann
authors.forename: Fotini
authors.initials: F
authors.lastname: Servetopoulou
authors.forename: Anne
authors.initials: A
authors.lastname: Letsch
authors.forename: Armin
authors.initials: A
authors.lastname: Philipp
authors.forename: Michael H
authors.initials: MH
authors.lastname: Foerster
authors.forename: Alexander
authors.initials: A
authors.lastname: Schmittel
authors.forename: Eckhard
authors.initials: E
authors.lastname: Thiel
authors.forename: Ulrich
authors.initials: U
authors.lastname: Keilholz
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology* / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D019496:Cancer Vaccines / Q000276:immunology* / Q000627:therapeutic use; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology* / Q000627:therapeutic use; D006433:Hemocyanins / Q000276:immunology* / Q000627:therapeutic use; D006801:Humans; D007251:Influenza, Human / Q000276:immunology; D008297:Male; D008545:Melanoma / Q000276:immunology / Q000628:therapy; D008875:Middle Aged; D014442:Monophenol Monooxygenase / Q000276:immunology*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology*; D014611:Vaccination
chemical_list: D000276:Adjuvants, Immunologic; D019496:Cancer Vaccines; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006433:Hemocyanins; D014442:Monophenol Monooxygenase; C032808:keyhole-limpet hemocyanin