Generation of cytotoxic T-cell responses with synthetic melanoma-associated peptides in vivo: implications for tumor vaccines with melanoma-associated antigens

Details

Serval ID
serval:BIB_70F532CF5FC5
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Generation of cytotoxic T-cell responses with synthetic melanoma-associated peptides in vivo: implications for tumor vaccines with melanoma-associated antigens
Journal
International Journal of Cancer
Author(s)
Jaeger  E., Bernhard  H., Romero  P., Ringhoffer  M., Arand  M., Karbach  J., Ilsemann  C., Hagedorn  M., Knuth  A.
ISSN
0020-7136 (Print)
Publication state
Published
Issued date
04/1996
Volume
66
Number
2
Pages
162-9
Notes
Journal Article --- Old month value: Apr 10
Abstract
Peptide epitopes derived from differentiation antigens of the melanocyte lineage have been identified in human melanomas and normal cultured melanocytes as targets for MHC-restricted cytotoxic T lymphocytes (CTL). Characterization of multiple CTL-defined antigenic determinants and the presence of corresponding precursor CTL open perspectives for the development of antigen-based vaccines. In the present study, we determined the CTL reactivity against melanoma-associated peptides derived from Melan A/MART-1, tyrosinase and gp100/Pmel17 in 10 HLA-A2+ melanoma patients and 10 healthy individuals. Then, we examined the immunological effects and toxicity of intradermal inoculation of synthetic melanoma-associated peptides. Six patients with advanced melanoma received weekly intradermal injections of 6 melanoma-associated peptides and the influenza matrix peptide as a control for 4 consecutive weeks. DTH reactions were observed in 5/6 patients at the injections sites of the tyrosinase signal peptide and of the influenza matrix peptide. No toxic side effects were observed. Changes in CTL reactivity after peptide vaccination were assessed by an MLPC assay for each peptide. Generation of peptide-specific CTL was documented against Melan A/MART-1-derived peptide epitopes, the tyrosinase signal peptide and the influenza matrix peptide after vaccination. A decreasing CTL response against the internal tyrosinase peptide was documented in 1 patient through the course of vaccination and a decrease in DTH reactions. No major tumor regressions were observed. Two patients with rapidly progressive disease before vaccination have shown disease stabilization since vaccinations started. In conclusion, our results demonstrate that peptide alone injected intradermally may generate antigen-specific DTH reactions and an increase of antigen-specific CTL reactivity.
Keywords
Adult Aged Amino Acid Sequence Antigens, Neoplasm/*immunology Cells, Cultured Female Humans Hypersensitivity, Delayed Injections, Intradermal Male Melanoma/*immunology Middle Aged Molecular Sequence Data Neoplasm Proteins/*immunology T-Lymphocytes, Cytotoxic/*immunology Vaccines/*immunology
Pubmed
Web of science
Open Access
Yes
Create date
28/01/2008 11:28
Last modification date
20/08/2019 14:29
Usage data