| Differential capacity of chaperone-rich lysates in cross-presenting human endogenous and exogenous melanoma differentiation antigens. | |
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MedLine Citation:
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PMID: 18608582 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The goal of immune-based tumor therapies is the activation of immune cells reactive against a broad spectrum of tumor-expressed antigens. Vaccines based on chaperone proteins appear promising as these proteins naturally exist as complexes with various protein fragments including those derived from tumor-associated antigens. Multi-chaperone systems are expected to have highest polyvalency as different chaperones can carry distinct sets of antigenic fragments. A free-solution isoelectric focusing (FS-IEF) technique was established to generate chaperone-rich cell lysates (CRCL). Results from murine systems support the contention that CRCL induce superior anti-tumor responses than single chaperone vaccines. We established an in vitro model for human melanoma to evaluate the capacity of CRCL to transfer endogenously expressed tumor antigens to the cross-presentation pathway of dendritic cells (DC) for antigen-specific T cell stimulation. CRCL prepared from human melanoma lines contained the four major chaperone proteins Hsp/Hsc70, Hsp90, Grp94/gp96 and calreticulin. The chaperones within the melanoma cell-derived CRCL were functionally active in that they enhanced cross-presentation of exogenous peptides mixed into the CRCL preparation. Superior activity was observed for Hsp70-rich CRCL obtained from heat-stressed melanoma cells. Despite the presence of active chaperones, melanoma cell-derived CRCL failed to transfer endogenously expressed melanoma-associated antigens to DC for cross-presentation and cytotoxic T cell (CTL) recognition, even after increasing intracellular protein levels of tumor antigen or chaperones. These findings reveal limitations of the CRCL approach regarding cross-presentation of endogenously expressed melanoma-associated antigens. Yet, CRCL may be utilized as vehicles to enhance the delivery of exogenous antigens for DC-mediated cross-presentation and T cell stimulation. |
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Authors:
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Elke Bleifuss; Henriette Bendz; Birgit Sirch; Sylvia Thompson; Anna Brandl; Valeria Milani; Michael W Graner; Ingo Drexler; Maria Kuppner; Emmanuel Katsanis; Elfriede Noessner; Rolf-Dieter Issels |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group Volume: 24 ISSN: 1464-5157 ISO Abbreviation: Int J Hyperthermia Publication Date: 2008 Dec |
Date Detail:
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Created Date: 2008-12-09 Completed Date: 2009-02-09 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8508395 Medline TA: Int J Hyperthermia Country: England |
Other Details:
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Languages: eng Pagination: 623-37 Citation Subset: IM |
Affiliation:
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Clinical Cooperation Group Hyperthermia, Helmholtz Zentrum München-German Research Center for Environmental Health, 81377 Munich, Germany. elke.bleifuss@gmx.de |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antigen Presentation / immunology Antigens, Differentiation / immunology* Antigens, Neoplasm / immunology* Biological Markers / metabolism Cancer Vaccines / immunology Cell Line, Tumor Cross-Priming / immunology* Dendritic Cells / immunology Hot Temperature Humans Interleukin-12 / immunology Melanoma / immunology*, pathology Molecular Chaperones / immunology* Monophenol Monooxygenase / metabolism T-Lymphocytes, Cytotoxic / immunology |
| Chemical | |
Reg. No./Substance:
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0/Antigens, Differentiation; 0/Antigens, Neoplasm; 0/Biological Markers; 0/Cancer Vaccines; 0/Molecular Chaperones; 187348-17-0/Interleukin-12; EC 1.14.18.1/Monophenol Monooxygenase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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