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Wild-type and modified gp100 peptide-pulsed dendritic cell vaccination of advanced melanoma patients can lead to long-term clinical responses independent of the peptide used.

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Lesterhuis, W Joost [] Schreibelt, Gerty [] Scharenborg, Nicole M [] Brouwer, H Marylène H [Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands] Gerritsen, Marie-Jeanne P [] Coulie, Pierre G. [UCL] Punt, Cornelis J A []

Dendritic cell (DC)-based immunotherapy is explored worldwide in cancer patients. Several strategies have been employed to load DC with antigen, including peptide loading. To increase immunogenicity of peptides, major histocompatibility complex (MHC) class I binding affinity and stability of peptide-MHC complexes at the cell surface may be improved by modification of the amino acid sequence. In this study, we compared the capacity of DC loaded with wild-type versus modified gp100 peptides with higher binding affinities to induce an immune and clinical response in advanced melanoma patients. Metastatic HLA-A2.1(+) melanoma patients were vaccinated intravenously (on average 25 × 10(6) DC) and intradermally (on average 11 × 10(6) DC) with mature DC loaded with keyhole limpet hemocyanin (KLH) together with tyrosinase peptide and either wild-type (15 patients) or modified (12 patients) gp100 peptides. All vaccinated patients showed a pronounced proliferative T cell or humoral response against KLH. Gp100-specific T cell responses were monitored in post-treatment delayed type hypersensitivity (DTH) skin biopsies by tetramer and functional analysis. Antigen-specific T cells were found in 2 of 15 patients vaccinated with wild-type gp100-loaded DC, versus 1 of 12 patients vaccinated with modified peptide-loaded DC. These three patients also had the best clinical response, with long-term (>8 years) complete responses in two patients, one in each group. We conclude that vaccination with peptide-loaded DC can result in long-term clinical responses in a minority of metastatic melanoma patients, and that the use of modified as compared to wild-type gp100 peptides for DC loading does not result in a relevant enhanced immune responses.

Document type Article de périodique (Journal article) – Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't
Access type Accès restreint
Publication date 2011
Language Anglais
Journal information "Cancer Immunology Immunotherapy" - Vol. 60, no. 2, p. 249-60 (2011)
Peer reviewed yes
issn 0340-7004
Publication status Publié
Affiliation Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands - Department of Medical Oncology
MESH Subject Adult ; Aged ; Male ; Melanoma - immunology, therapy ; Middle Aged ; T-Lymphocytes, Cytotoxic - immunology ; Treatment Outcome ; Young Adult ; gp100 Melanoma Antigen - genetics, immunology ; Antigens, Neoplasm - immunology ; Cancer Vaccines - adverse effects, immunology, therapeutic use ; Cell Proliferation ; Cytokines - biosynthesis ; Dendritic Cells - immunology, transplantation ; Disease Progression ; Female ; Humans
Links
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Bibliographic reference Lesterhuis, W Joost ; Schreibelt, Gerty ; Scharenborg, Nicole M ; Brouwer, H Marylène H ; Gerritsen, Marie-Jeanne P ; et. al. Wild-type and modified gp100 peptide-pulsed dendritic cell vaccination of advanced melanoma patients can lead to long-term clinical responses independent of the peptide used.. In: Cancer Immunology Immunotherapy, Vol. 60, no. 2, p. 249-60 (2011)
Permanent URL http://hdl.handle.net/2078/88204