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

Open Access
Publisher Website
Google Scholar
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.

This publication has 29 references indexed in Scilit: