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01-08-2004 | Original Article

Analysis of T-cell responses in metastatic melanoma patients vaccinated with dendritic cells pulsed with tumor lysates

Authors: Marieke Griffioen, Martina Borghi, Peter I. Schrier, Susanne Osanto, Dirk Schadendorf

Published in: Cancer Immunology, Immunotherapy | Issue 8/2004

Abstract

In melanoma patients, CD8⁺cytotoxic T cells have been found recognizing self-proteins of which the expression is restricted to the melanocytic lineage. These melanocyte differentiation antigens are expressed in normal melanocytes as well as in 80–100% of primary and metastatic melanoma. In this report, six HLA-A*0201–subtyped metastatic melanoma patients vaccinated with dendritic cells (DCs) pulsed with autologous tumor lysates and keyhole limpet hemocyanin (KLH) were screened for the presence of CD8⁺ T cells specific for three HLA-A*0201–binding peptides derived from the melanosomal antigens MART-1/Melan-A, gp100, and tyrosinase. For this purpose, nonstimulated as well as in vitro peptide-stimulated peripheral blood mononuclear cells (PBMCs) were tested for peptide-specific IFN-γ release by enzyme-linked immunosorbent spot (ELISpot) assays. Furthermore, expression of the melanosomal antigens MART-1/Melan-A, gp100, and tyrosinase in tumor lesions was analyzed by immunohistochemistry before and after vaccination. We also used the ELISpot technique to investigate whether KLH-specific T cells were induced and whether these cells released type 1 (IFN-γ) and/or type 2 (IL-13) cytokines. Our data show induction of CD8⁺ T cells specific for the melanosomal peptides MART-1/Melan-A_27–35 or tyrosinase_1–9,as well as IFN-γ–releasing KLH-specific T cells, in two of six vaccinated melanoma patients, but do not support an association between the induction of these T cells and clinical responses.

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Title: Analysis of T-cell responses in metastatic melanoma patients vaccinated with dendritic cells pulsed with tumor lysates
Authors: Marieke Griffioen
Martina Borghi
Peter I. Schrier
Susanne Osanto
Dirk Schadendorf
Publication date: 01-08-2004
Publisher: Springer-Verlag
Published in: Cancer Immunology, Immunotherapy / Issue 8/2004
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-004-0514-z

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