Document Detail


A new strategy to induce effective antitumour response in vitro and in vivo.
MedLine Citation:
PMID:  18782257     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
To induce Her2-specific cell immune response, we used xenogeneic antigen rat neu L2-S2 domains as the vaccine antigen. The antigenic protein was engineered as a chimeric protein with human IgG1 Fc region (neu-Fc). Neu-Fc could stimulate the cell proliferation in mixed lymphocyte reaction effectively. Simultaneous neu-Fc and IFN-gamma stimulation dramatically elevated IL-12 secretion and reduced IL-10 production in PBMC. To further augment the activating effects on Th1-type response, Bacille Calmette-Guerin (BCG) was utilized as a non-specific stimulus. Neu-Fc, IFN-gamma and BCG costimulation exhibited the most conspicuous effects on the reversal of the Th1-type inhibitory effects by MCF-7 cell supernatant compared with neu-Fc alone or IFN-gamma and BCG costimulation. The lytic activity of effector cells to Her2 overexpressing cells was greatly promoted by neu-Fc, IFN-gamma and BCG stimulation simultaneously. Neu-Fc led to considerable retardation in EMT6/Her2 tumour growth in Balb/c mice. IFN-gamma and BCG efficiently enhanced the antitumour activity. A large amount of inflammatory cells were found to be accumulated in the tumour tissues or surrounded tumours in mice treated with neu-Fc, IFN-gamma and BCG but no inflammatory cell infiltration was observed in control tumours, indicating that the strategy is potent enough to support the initiation and propagation of tumour-specific immune response in an established tumour and generate a proinflammatory environment.
Authors:
M Wang; Z Xie; M Shi; H Lu; M Yu; M Hu; F Lu; Y Ma; B Shen; N Guo
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Scandinavian journal of immunology     Volume:  68     ISSN:  1365-3083     ISO Abbreviation:  Scand. J. Immunol.     Publication Date:  2008 Sep 
Date Detail:
Created Date:  2008-09-10     Completed Date:  2008-10-07     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  0323767     Medline TA:  Scand J Immunol     Country:  England    
Other Details:
Languages:  eng     Pagination:  287-96     Citation Subset:  IM    
Affiliation:
Institute of Basic Medical Sciences, Beijing, China.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antigens, Heterophile / administration & dosage,  therapeutic use*
BCG Vaccine / administration & dosage,  pharmacology*,  therapeutic use*
Cell Line, Tumor / metabolism
Culture Media, Conditioned / pharmacology
Cytotoxicity, Immunologic / drug effects*
Female
Glycoproteins / metabolism
Histocompatibility Antigens Class I / metabolism
Humans
Inflammation / pathology
Injections, Intravenous
Injections, Subcutaneous
Interferon-gamma / administration & dosage,  pharmacology*,  therapeutic use*
Interleukin-10 / biosynthesis
Interleukin-12 / antagonists & inhibitors*,  metabolism
Leukocytes, Mononuclear / drug effects,  immunology,  metabolism
Mice
Mice, Inbred BALB C
Monocytes / drug effects*,  immunology*,  metabolism
Neoplasms, Experimental / pathology,  therapy
Receptors, Fc / metabolism
Recombinant Fusion Proteins / administration & dosage,  pharmacology*,  therapeutic use*
Chemical
Reg. No./Substance:
0/Antigens, Heterophile; 0/BCG Vaccine; 0/Culture Media, Conditioned; 0/Erbb2 protein, rat; 0/Fc receptor, neonatal; 0/Glycoproteins; 0/Histocompatibility Antigens Class I; 0/Receptors, Fc; 0/Recombinant Fusion Proteins; 130068-27-8/Interleukin-10; 187348-17-0/Interleukin-12; 82115-62-6/Interferon-gamma

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