| Induction of proapoptotic antibodies to triple-negative breast cancer by vaccination with TRAIL death receptor DR5 DNA. | |
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MedLine Citation:
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PMID: 22419388 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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TNF-related apoptosis-inducing ligand receptor 2 [TRAIL-R2 or death receptor 5 (DR5)] is expressed at elevated levels in a broad range of solid tumors to mediate apoptotic signals from TRAIL or agonist antibodies. We tested the hypothesis that DR5 DNA vaccination will induce proapoptotic antibody to trigger apoptosis of tumor cells. BALB/c mice were electrovaccinated with DNA-encoding wild-type human DR5 (phDR5) or its derivatives. Resulting immune serum or purified immune IgG induced apoptosis in triple-negative breast cancer (TNBC) cells, which were also TRAIL sensitive. The proapoptotic activity of immune serum at dilutions of 0.5-2% was comparable to that of 1-2 μg/ml of TRAIL. Apoptotic activity of immune serum was enhanced by antibody crosslinking. Apoptotic cell death induced by anti-DR5 antibody was shown by the cleavage of PARP and caspase-3. In contrast, immune serum had no effect on the proliferation of activated human T cells, which expressed low levels of DR5. In vivo, hDR5 reactive immune serum prevented growth of SUM159 TNBC cells in severe combined immune-deficient mice. DR5-specific IFN-γ-secreting T cells were also induced by DNA vaccination. Furthermore, the feasibility to overcome immune tolerance to self DR5 was shown by the induction of mouse DR5-binding antibody after electrovaccination of BALB/c mice with pmDR5ectm-Td1 encoding a fusion protein of mouse DR5 and an immunogenic fragment of tetanus toxin. These findings support DR5 as a promising vaccine target for controlling TNBC and other DR5-positive cancers. |
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Authors:
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Marie P Piechocki; Gen Sheng Wu; Richard F Jones; Jennifer B Jacob; Heather Gibson; Stephen P Ethier; Judith Abrams; Hideo Yagita; K Venuprasad; Wei-Zen Wei |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S. Date: 2012-04-24 |
Journal Detail:
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Title: International journal of cancer. Journal international du cancer Volume: 131 ISSN: 1097-0215 ISO Abbreviation: Int. J. Cancer Publication Date: 2012 Dec |
Date Detail:
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Created Date: 2012-09-26 Completed Date: 2013-03-08 Revised Date: 2013-04-16 |
Medline Journal Info:
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Nlm Unique ID: 0042124 Medline TA: Int J Cancer Country: United States |
Other Details:
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Languages: eng Pagination: 2562-72 Citation Subset: IM |
Copyright Information:
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Copyright © 2012 UICC. |
Affiliation:
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Karmanos Cancer Institute, Wayne State University, Detroit, MI 48201, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antibodies, Neoplasm / biosynthesis*, immunology Apoptosis / genetics, immunology* BALB 3T3 Cells Breast Neoplasms / genetics, immunology*, therapy Cancer Vaccines / administration & dosage*, genetics, immunology Cell Growth Processes / immunology Cell Line, Tumor Female Humans Immune Sera / immunology Immunoglobulin G / immunology Interferon-gamma / immunology Mice Mice, SCID NIH 3T3 Cells Receptors, TNF-Related Apoptosis-Inducing Ligand / genetics, immunology* T-Lymphocytes / immunology Vaccines, DNA / administration & dosage*, genetics, immunology |
| Grant Support | |
ID/Acronym/Agency:
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CA 76340/CA/NCI NIH HHS; CA125680/CA/NCI NIH HHS; R01 CA076340/CA/NCI NIH HHS; R01 CA076340-11A2/CA/NCI NIH HHS; R01 CA125680-05/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antibodies, Neoplasm; 0/Cancer Vaccines; 0/Immune Sera; 0/Immunoglobulin G; 0/Receptors, TNF-Related Apoptosis-Inducing Ligand; 0/Vaccines, DNA; 82115-62-6/Interferon-gamma |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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