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Effects of granulocyte‐macrophage colony‐stimulating factor and foreign helper protein as immunologic adjuvants on the T‐cell response to vaccination with tyrosinase peptides
Author(s) -
Scheibenbogen Carmen,
Schadendorf Dirk,
Bechrakis Nikolaos E.,
Nagorsen Dirk,
Hofmann Udo,
Servetopoulou Fotini,
Letsch Anne,
Philipp Armin,
Foerster Michael H.,
Schmittel Alexander,
Thiel Eckhard,
Keilholz Ulrich
Publication year - 2003
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.10961
Subject(s) - elispot , adjuvant , immunogenicity , tyrosinase , immunology , medicine , vaccination , mhc class i , mhc class ii , antigen , t cell , major histocompatibility complex , immune system , biology , biochemistry , enzyme
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.