Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
21
pubmed:dateCreated
2002-10-14
pubmed:abstractText
Interleukin-18 is a potent cytokine expressed early in the immune response following cleavage in activated composes. We have investigated the in vivo antitumor effects of intratumoral (i.t.) administration of an adenoviral vector expressing biologically active murine interleukin (IL)-18 (Ad.PTH.IL-18). Substantial antitumor effects were observed when established MCA205 fibrosarcoma was treated in syngeneic immunocompetent mice with intratumoral injection of Ad.PTH.IL-18 (P = 0.0025 versus control vector treatment), generating potent cytotoxic T lymphocytes (CTLs) in culture. In contrast, the antitumor effect was absent, and cytotoxic activity was significantly less (P = 0.021) in gld mice (Fas ligand deficient). To enhance the in vivo antitumor activity of the treatment using Ad.PTH.IL-18, we co-injected immature DC and Ad.PTH.IL-18 i.t. into established, day 7 MCA205 fibrosarcoma and MC38 adenocarcinoma. Co-injection of both Ad.PTH.IL-18 and DC was associated with complete abrogation of injected tumors. Furthermore, the antitumor effects were also observed on distant tumors inoculated i.d. in the contralateral flank of the animal. The induced cytolytic activity was tumor-specific and MHC class I-restricted. As we have previously demonstrated in vitro (Tanaka F et al, Cancer Res 2000; 60: 4838-4844) and consistent with these findings in vivo, NK, T and dendritic cells coactivately mediate the IL-18 enhanced antitumor effect. This study suggests that the coactivate strategy could be used in the clinical setting to treat patients with cancer. do
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0969-7128
pubmed:author
pubmed:issnType
Print
pubmed:volume
9
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1480-6
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:12378411-Adenosarcoma, pubmed-meshheading:12378411-Adenoviridae, pubmed-meshheading:12378411-Animals, pubmed-meshheading:12378411-Dendritic Cells, pubmed-meshheading:12378411-Fas Ligand Protein, pubmed-meshheading:12378411-Fibrosarcoma, pubmed-meshheading:12378411-Gene Therapy, pubmed-meshheading:12378411-Genetic Vectors, pubmed-meshheading:12378411-Immunotherapy, Adoptive, pubmed-meshheading:12378411-Injections, Intralesional, pubmed-meshheading:12378411-Interleukin-12, pubmed-meshheading:12378411-Interleukin-18, pubmed-meshheading:12378411-Membrane Glycoproteins, pubmed-meshheading:12378411-Mice, pubmed-meshheading:12378411-Mice, Inbred C57BL, pubmed-meshheading:12378411-Mice, Mutant Strains, pubmed-meshheading:12378411-Neoplasm Transplantation, pubmed-meshheading:12378411-T-Lymphocytes, Cytotoxic, pubmed-meshheading:12378411-Tumor Cells, Cultured
pubmed:year
2002
pubmed:articleTitle
Therapeutic and specific antitumor immunity induced by co-administration of immature dendritic cells and adenoviral vector expressing biologically active IL-18.
pubmed:affiliation
Department of Surgery, University of Pittsburgh School of Medicine, PA, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't