Granulocyte-macrophage-colony-stimulating factor enhances immune responses to melanoma-associated peptides in vivo
Elke Jäger,Mark Ringhoffer,Hans Peter Dienes,Michael Arand,Julia Karbach,Dirk Jäger,Christiane Ilsemann,Manfred Hagedorn,Franz Oesch,Alexander Knuth +9 more
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TL;DR: It is concluded that systemic GM‐CSF enhances immune responses to melanoma‐associated peptides and supports CTL‐mediated tumor rejection in vivo.
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Abstract: 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 antigen-targeted vaccines. In the present study, we determined CTL reactivity against melanoma-associated peptides derived from Melan A/MART-1, tyrosinase, and gp100/Pmel17 in 3 HLA-A2+ melanoma patients. Then, we assessed the immune responses to synthetic melanoma-associated peptides injected intradermally. 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. Immunohistochemical characterization of DTH-constituting elements revealed infiltrates of CD4+ and CD8+ T lymphocytes and strong expression of IL-2 and gammaIFN, suggesting the activation of CD4+ ThI and CD8+ CTL by peptides presented by MHC-class-I 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.
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Granulocyte-macrophage colony-stimulating factor alone or with dacarbazine in metastatic melanoma: a randomized phase II trial.
Alain Ravaud,M. Delaunay,Christine Chevreau,V. Coulon,Marc Debled,C Bret-Dibat,F Courbon,Norbert Gualde,B Nguyen Bui +8 more
TL;DR: GM-CSF alone or in association with DTIC did not induce any antitumoural activity with subsequent toxicity in metastatic melanoma in first line randomized phase II, and no objective response was obtained.
Novel immunologic approaches to the management of malignant melanoma.
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TL;DR: The rationale for and the results of a number of clinical trials of peptide vaccines for melanoma are summarized, suggesting that immune and clinical responses can be seen in those with metastatic and resected disease using a variety of surrogate assays.
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TL;DR: Efficient therapeutic vaccination should aim at boosting naturally occurring anti-tumor responses and at sustaining a large contingent of tumor antigen-specific and fully functional effector T cells at tumor sites.
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Quantitative assessment of the expression of melanoma-associated antigens by non-competitive reverse transcription polymerase chain reaction
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