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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2000-8-10
pubmed:abstractText
Suicide gene therapy has been studied intensively for the treatment of cancer. A limited antitumoral effect was obtained by intratumoral injection of adenovirus harboring Escherichia coli cytosine deaminase gene (AdCD) in tumor-bearing mice followed by continuous administration of 5-fluorocytosine (5FC). To address the drawbacks of the limited potential for the induction of antitumoral immunity by CD suicide gene therapy, we hypothesized that antigen-presenting cells (APCs) might contribute to the efficient induction of an antitumoral immune response in tumor-bearing mice undergoing suicide gene therapy. We preinjected the mice with murine stem cell factor (SCF)-encoding adenovirus (AdSCF) and murine granulocyte-macrophage colony-stimulating factor (GM-CSF)-encoding adenovirus (AdGM-CSF); after 7 days, the mice were inoculated with CT26 colon adenocarcinoma. AdCD was injected intratumorally into tumor-bearing mice followed by 5FC administration. The results showed that AdSCF/AdGM-CSF treatment could increase the number, surface molecule expression, and function of APCs efficiently. A more significant growth inhibition of established tumors and a prolongation of the survival period were observed in tumor-bearing mice after AdSCF/AdGM-CSF pretreatment in combination with AdCD/5FC therapy when compared with mice treated with AdSCF or AdGM-CSF in combination with AdCD/5FC, or AdCD/5FC alone (P < .01). Cytotoxic T-lymphocyte activity was induced efficiently after the combined therapy, and mRNA of tumor necrosis factor-alpha, interleukin-4, interferon-gamma, and interleukin-2 was present in the tumor mass after combined therapy, suggesting that a more potent antitumoral response was induced by enhanced APCs. Our results demonstrated that AdSCF/AdGM-CSF pretreatment could activate APCs, and that these APCs could present the tumor antigens released from AdCD/5FC-killed tumor cells and activate the antitumoral response of the host, thus increasing the therapeutic efficiency of suicide gene therapy.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0929-1903
pubmed:author
pubmed:issnType
Print
pubmed:volume
7
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
177-86
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:10770625-Adenoviridae, pubmed-meshheading:10770625-Adjuvants, Immunologic, pubmed-meshheading:10770625-Animals, pubmed-meshheading:10770625-Antigen-Presenting Cells, pubmed-meshheading:10770625-Cancer Vaccines, pubmed-meshheading:10770625-Cell Count, pubmed-meshheading:10770625-Cell Differentiation, pubmed-meshheading:10770625-Cell Line, pubmed-meshheading:10770625-Combined Modality Therapy, pubmed-meshheading:10770625-Cytokines, pubmed-meshheading:10770625-Cytosine Deaminase, pubmed-meshheading:10770625-Female, pubmed-meshheading:10770625-Gene Therapy, pubmed-meshheading:10770625-Gene Transfer Techniques, pubmed-meshheading:10770625-Granulocyte-Macrophage Colony-Stimulating Factor, pubmed-meshheading:10770625-Humans, pubmed-meshheading:10770625-Injections, Intraperitoneal, pubmed-meshheading:10770625-Mice, pubmed-meshheading:10770625-Mice, Inbred BALB C, pubmed-meshheading:10770625-Mice, Inbred C57BL, pubmed-meshheading:10770625-Nucleoside Deaminases, pubmed-meshheading:10770625-Stem Cell Factor, pubmed-meshheading:10770625-Tumor Cells, Cultured
pubmed:year
2000
pubmed:articleTitle
Enhanced antitumoral effect of adenovirus-mediated cytosine deaminase gene therapy by induction of antigen-presenting cells through stem cell factor/granulocyte-macrophage colony-stimulating factor gene transfer.
pubmed:affiliation
Department of Immunology, Second Military Medical University, Shanghai, People's Republic of China. caoxt@public3.sta.net.cn
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't