Document Detail


Antitumor effects of combined granulocyte macrophage colony stimulating factor and macrophage inflammatory protein-3 alpha plasmid DNA.
MedLine Citation:
PMID:  20804501     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Dendritic cells (DC) are critical for priming adaptive immune responses to foreign antigens. However, the feasibility of harnessing these cells in vivo to optimize the antitumor effects has not been fully explored. The authors investigated a novel therapeutic approach that involves delivering synergistic signals that both recruit and expand DC populations at sites of intratumoral injection. More specifically, the authors examined whether the co-administration of plasmids encoding the chemokine macrophage inflammatory protein-3 alpha (pMIP3α) and plasmid encoding the granulocyte macrophage colony stimulating factor (pGM-CSF; a DC-specific growth factor) can recruit, expand and activate large numbers of DC at sites of intratumoral injection. It was found that the administration of pGM-CSF and pMIP3α resulted in dramatic recruitment and expansion of DC at these sites and in draining lymph nodes. Furthermore, treatment with pGM-CSF and pMIP3α generated the strongest MUC1-associated CD8+ T-cell immune responses in draining lymph nodes and in tumors, produced the greatest antitumor effects and enhanced survival rates more than pcDNA3.1, pGM-CSF alone and pMIP3α alone. It was also found that pGM-CSF plus pMIP3α generated the strongest MUC1-associated CD4+ T-cell immune responses in draining lymph nodes and in tumors. The findings of the present study suggest that the recruitment and activation of DC in vivo due to the synergistic actions of pGM-CSF and pMIP3α presents a potentially feasible means of controlling immunogenic malignancies and provides a basis for the development of novel immunotherapeutic treatments.
Authors:
Yun Choi; Chul W Kim
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cancer science     Volume:  101     ISSN:  1349-7006     ISO Abbreviation:  Cancer Sci.     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-10-18     Completed Date:  2010-11-29     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101168776     Medline TA:  Cancer Sci     Country:  England    
Other Details:
Languages:  eng     Pagination:  2341-50     Citation Subset:  IM    
Copyright Information:
© 2010 Japanese Cancer Association.
Affiliation:
Department of Pathology, Seoul National University College of Medicine, Seoul, Korea.
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MeSH Terms
Descriptor/Qualifier:
Animals
CD4-Positive T-Lymphocytes / immunology,  metabolism
CD8-Positive T-Lymphocytes / immunology,  metabolism
Cell Count
Cell Line, Tumor
Chemokine CCL20 / genetics,  immunology*,  metabolism
Dendritic Cells / immunology*
Enzyme-Linked Immunosorbent Assay
Feasibility Studies
Female
Granulocyte-Macrophage Colony-Stimulating Factor / genetics,  immunology*,  metabolism
Humans
Interferon-gamma / metabolism
Mice
Mice, Inbred C57BL
Mucin-1 / genetics,  immunology
Neoplasms, Experimental / immunology*,  pathology,  therapy
Plasmids / administration & dosage,  genetics
Reverse Transcriptase Polymerase Chain Reaction
Survival Analysis
Tumor Burden / immunology
Chemical
Reg. No./Substance:
0/Chemokine CCL20; 0/Mucin-1; 82115-62-6/Interferon-gamma; 83869-56-1/Granulocyte-Macrophage Colony-Stimulating Factor

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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