Granulocyte-macrophage-colony-stimulating factor enhances immune responses to melanoma-associated peptides in vivo

✍ Scribed by Elke Jäger; Mark Ringhoffer; Hans Peter Dienes; Michael Arand; Julia Karbach; Dirk Jäger; Christiane Ilsemann; Manfred Hagedorn; Franz Oesch; Alexander Knuth

• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: French
• Weight: 931 KB
• Volume: 67
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/(sici)1097-0215(19960703)67:1<54::aid-ijc11>3.0.co;2-c

✦ Synopsis

Peptide epitopes derived from differentiation antigens of the melanocyte lineage were recently identified in human melanomas as targets for MHC-restricted cytotoxic T lymphocytes (CTL). The characterization of multiple CTL-defined antigenic determinants has opened possibilities of development of antigentargeted vaccines. In the present study, we determined CTL reactivity against melanoma-associated peptides derived from Melan A/MART-I, tyrosinase, and gp IOO/Pmel I7 in 3 HLA-A2+ melanoma patients. Then, we assessed the immune responses to synthetic melanoma-associated peptides injected intraderma-Ily. After 3 cycles of immunization with peptide alone, we used systemic GM-CSF as an adjuvant during the fourth cycle of immunization. Enhanced DTH reactions and CD8+ CTL responses were observed after treatment with systemic GM-CSF. lmmunohistochemical characterization of DTH-constituting elements revealed infiltrates of CD4+ and CD8+ T lymphocytes and strong expression of IL-2 and yIFN, suggesting the activation of CD4+ Th I and CD8+ CTL by peptides presented by MHC-class4 molecules of dermal APC. Objective tumor regression was documented in all patients. We conclude that systemic GM-CSF enhances immune responses to melanoma-associated peptides and supports CTL-mediated tumor rejection in vivo.