Document Detail


Type-1 polarized dendritic cells loaded with apoptotic prostate cancer cells are potent inducers of CD8(+) T cells against prostate cancer cells and defined prostate cancer-specific epitopes.
MedLine Citation:
PMID:  20717900     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: In order to develop improved vaccines for patients with recurrent prostate cancer (PCa), we tested the feasibility of using type-1 polarized dendritic cells (αDC1s) to cross-present antigens from allogeneic PCa cells and to induce functional CD8(+) T cell responses against PCa cells and against defined MHC class I-restricted PCa-relevant epitopes.
METHODS: Monocyte-derived DCs from PCa patients were matured using the "standard" cytokine cocktail (IL-1β/TNFα/IL-6/PGE₂) or using the αDC1-polarizing cocktail (IL-1β/TNFα/IFNα/IFNγ/poly-I:C), loaded with UV-irradiated LNCaP cells, and used to sensitize autologous CD8(+) T cells.
RESULTS: αDC1s from PCa patients secreted 10-30 times higher levels of IL-12p70 than sDCs. Importantly this elevated capacity for IL-12p70 secretion was not inhibited by loading with apoptotic tumor cells. Compared to standard DCs, αDC1s induced higher numbers of CD8(+) T cells capable of recognizing both the original PCa cells as well as another PCa cell line, DU145, in MHC class I-restricted fashion. Furthermore, αDC1s induced higher numbers of CD8(+) T cells recognizing defined PCa-specific class I-restricted peptide epitopes of prostate-specific antigen and prostatic acid phosphatase: PAP(135-143) (average 49-fold higher), PAP(112-120) (average 24-fold), PSA(141-150) (average 5.5-fold), and PSA(146-154) (average 11-fold).
CONCLUSION: Type-1 polarization of GM-CSF/IL-4-generated DCs enhances their ability to present allogeneic tumor cells and to induce CD8(+) T cells recognizing different PCa cells and multiple defined PCa-specific epitopes. These observations help to develop improved immunotherapies of PCa for patients with different HLA types and lacking autologous tumor material.
Authors:
Eva Wieckowski; Gurkamal S Chatta; Robbie M Mailliard; William Gooding; Karolina Palucka; Jacques Banchereau; Pawel Kalinski
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2010-08-17
Journal Detail:
Title:  The Prostate     Volume:  71     ISSN:  1097-0045     ISO Abbreviation:  Prostate     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2010-12-24     Completed Date:  2011-01-24     Revised Date:  2014-09-21    
Medline Journal Info:
Nlm Unique ID:  8101368     Medline TA:  Prostate     Country:  United States    
Other Details:
Languages:  eng     Pagination:  125-33     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Wiley-Liss, Inc.
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MeSH Terms
Descriptor/Qualifier:
Alkaline Phosphatase / analysis
CD8-Positive T-Lymphocytes / immunology*
Cancer Vaccines / immunology,  therapeutic use*
Cell Line, Tumor
Dendritic Cells / immunology*
Epitopes, T-Lymphocyte / immunology*
Flow Cytometry
Humans
Immunotherapy, Adoptive / methods*
Interleukin-12 / biosynthesis,  immunology
Male
Prostate-Specific Antigen / analysis
Prostatic Neoplasms / blood,  immunology*,  therapy*
Th1 Cells / immunology
Grant Support
ID/Acronym/Agency:
CA095128/CA/NCI NIH HHS; CA101944/CA/NCI NIH HHS; CA10373005/CA/NCI NIH HHS; CA114931/CA/NCI NIH HHS; P01 CA101944/CA/NCI NIH HHS; P01 CA101944-030002/CA/NCI NIH HHS; P01 CA101944-040002/CA/NCI NIH HHS; P01 CA101944-050002/CA/NCI NIH HHS; P20 CA103730-05/CA/NCI NIH HHS; R01 CA095128/CA/NCI NIH HHS; R01 CA095128-03/CA/NCI NIH HHS; R01 CA095128-04/CA/NCI NIH HHS; R01 CA095128-05A1/CA/NCI NIH HHS; R21 CA114931/CA/NCI NIH HHS; R21 CA114931-01/CA/NCI NIH HHS; R21 CA114931-02/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Cancer Vaccines; 0/Epitopes, T-Lymphocyte; 187348-17-0/Interleukin-12; EC 3.1.3.1/Alkaline Phosphatase; EC 3.4.21.77/Prostate-Specific Antigen
Comments/Corrections

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