| Bacillus Calmette-Gu?rin cell-wall skeleton enhances the killing activity of cytotoxic lymphocyte-activated human dendritic cells transduced with the prostate-specific antigen gene. | |
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MedLine Citation:
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PMID: 20063450 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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To determine whether dendritic cells (DC) transduced with the prostate-specific antigen (PSA) gene can induce PSA-specific cytotoxic lymphocytes (CTL) against prostate cancer cells, and whether bacillus Calmette-Gu?rin (BCG) cell-wall skeleton (CWS) can enhance the maturation of DC-PSA and the killing activity of subsequently induced PSA-specific CTL. MATERIALS AND METHODS; We generated an adenovirus encoding the PSA gene (AxCA-PSA) using the cosmid-terminal protein complex method. DC were infected with AxCA-PSA using the centrifugal method. The ability of CTL to lyse target cells expressing PSA, i.e the PSA-positive prostate cancer cell line, LNCap, and PSA-transduced autologous phytohaemagglutinin (PHA) blasts expressing PSA, was assessed using the 51Cr-release assay. The maturation of DC-PSA stimulated by BCG-CWS was assayed by flow cytometry. The cytotoxic activity enhanced by BCG-CWS was assessed by the 51Cr-release assay. RESULTS: DC-PSA induced PSA-specific CTL with 85% cytotoxic activity against LNCaP (effector: target ratio, E:T, of 50:1). However, the cytotoxic activity against PSA-negative cells was very low. Anti-CD8 and anti-major histocompatibility (MHC) class I antibodies blocked PSA-specific cytotoxicity. The PSA-specific killing was reproducible against autologous PHA blast cells expressing PSA, independently of human leukocyte antigen haplotype. Furthermore, the combination of DC-PSA with BCG-CWS remarkably enhanced the PSA-specific cytotoxicity against PHA blasts expressing PSA (15-30% at an E:T ratio of 50:1). CONCLUSION: These findings suggest that DC-PSA can induce MHC class I-restricted PSA-specific CD8+ CTL responses and that DC-PSA matured by BCG-CWS enhance PSA-specific cytotoxicity. The combination of DC-PSA with BCG-CWS might be a useful approach for treating advanced prostate cancer. |
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Authors:
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Reona Fujii; Makoto Iwahashi; Kazuro Kikkawa; Takeshi Inagaki; Yasuo Kohjimoto; Toshiyasu Ojima; Takashi Mori; Tomomi Kuramoto; Satoshi Nishizawa; Ichiro Azuma; Hiroki Yamaue; Toshiaki Shinka; Isao Hara |
Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: BJU international Volume: 104 ISSN: 1464-410X ISO Abbreviation: BJU Int. Publication Date: 2009 Dec |
Date Detail:
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Created Date: 2010-01-08 Completed Date: 2010-02-17 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 100886721 Medline TA: BJU Int Country: England |
Other Details:
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Languages: eng Pagination: 1766-73 Citation Subset: IM |
Affiliation:
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Departments of Urology, Wakayama Medical University, Wakayama, Japan. |
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| MeSH Terms | |
Descriptor/Qualifier:
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Adenoviridae
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genetics Antigens, CD8 / immunology Cell Line, Tumor Cell Wall Skeleton / immunology, pharmacology* Dendritic Cells / immunology* Enzyme-Linked Immunosorbent Assay Flow Cytometry Gene Therapy / methods Genetic Vectors Histocompatibility Antigens Class I / immunology Humans Immunotherapy / methods Male Mycobacterium bovis* Prostate-Specific Antigen / genetics* Prostatic Neoplasms / therapy* T-Lymphocytes, Cytotoxic / physiology* Transduction, Genetic |
| Chemical | |
Reg. No./Substance:
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0/Antigens, CD8; 0/Cell Wall Skeleton; 0/Histocompatibility Antigens Class I; EC 3.4.21.77/Prostate-Specific Antigen |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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