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Generation of cytotoxic T‐cell responses with synthetic melanoma‐associated peptides in vivo : Implications for tumor vaccines with melanoma‐associated antigens
Author(s) -
Jäeger Elke,
Bernhard Helga,
Romero Pedro,
Ringhoffer Mark,
Arand Michael,
Karbach Julia,
Ilsemann Christiane,
Hagedorn Manfred,
Knuth Alexander
Publication year - 1996
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/(sici)1097-0215(19960410)66:2<162::aid-ijc4>3.0.co;2-0
Subject(s) - melanoma , cytotoxic t cell , in vivo , antigen , immunology , cancer research , medicine , cytotoxicity , biology , virology , in vitro , genetics
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‐I, tyrosinase and gp100/Pme117 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 injection 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‐I‐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. © 1996 Wiley‐Liss, Inc.