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.
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Authors | Sherven Sharma, Raj K Batra, Seok Chul Yang, Sven Hillinger, Li Zhu, Kimberly Atianzar, Robert M Strieter, Karen Riedl, Min Huang, Steven M Dubinett |
Journal | Human gene therapy
(Hum Gene Ther)
Vol. 14
Issue 16
Pg. 1511-24
(Nov 01 2003)
ISSN: 1043-0342 [Print] United States |
PMID | 14577913
(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.)
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Chemical References |
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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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