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Interleukin-7 gene-modified dendritic cells reduce pulmonary tumor burden in spontaneous murine bronchoalveolar cell carcinoma.

Abstract
The antitumor efficiency of dendritic cells transduced with an adenovirus vector expressing interleukin (IL)-7 (DC-AdIL-7) was evaluated in a murine model of spontaneous bronchoalveolar cell carcinoma. These transgenic mice (CC-10 TAg), expressing the SV40 large T antigen under the Clara cell promoter, develop bilateral multifocal pulmonary adenocarcinomas and die at 4 months as a result of progressive pulmonary tumor burden. Injection of DC-AdIL-7 in the axillary lymph node region (ALNR) weekly for 3 weeks led to a marked reduction in tumor burden with extensive lymphocytic infiltration of the tumors and enhanced survival. The antitumor responses were accompanied by the enhanced elaboration of interferon (IFN)-gamma and IL-12 as well as an increase in the antiangiogenic chemokines, IFN-gamma-inducible protein 10 (IP-10/CXCL10) and monokine induced by IFN-gamma (MIG/CXCL9). In contrast, production of the immunosuppressive mediators IL-10, transforming growth factor (TGF)-beta, prostaglandin E(2) (PGE(2)), and the proangiogenic modulator vascular endothelial growth factor (VEGF) decreased in response to DC-AdIL-7 treatment. Significant reduction in tumor burden in a model in which tumors develop in an organ-specific manner provides a strong rationale for further evaluation of DC-AdIL-7 in regulation of tumor immunity and its use in lung cancer genetic immunotherapy.
AuthorsSherven Sharma, Raj K Batra, Seok Chul Yang, Sven Hillinger, Li Zhu, Kimberly Atianzar, Robert M Strieter, Karen Riedl, Min Huang, Steven M Dubinett
JournalHuman gene therapy (Hum Gene Ther) Vol. 14 Issue 16 Pg. 1511-24 (Nov 01 2003) ISSN: 1043-0342 [Print] United States
PMID14577913 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Interleukin-7
Topics
  • Adenocarcinoma, Bronchiolo-Alveolar (immunology, therapy)
  • Adenoviridae (genetics)
  • Animals
  • Dendritic Cells (immunology)
  • Genetic Vectors
  • Immunotherapy, Adoptive
  • Interleukin-7 (genetics)
  • Lung Neoplasms (immunology, therapy)
  • Lymph Nodes (immunology)
  • Mice
  • Mice, Transgenic
  • Remission Induction
  • Transduction, Genetic

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