Interleukin-7 gene-modified dendritic cells reduce pulmonary tumor burden in spontaneous murine bronchoalveolar cell carcinoma.
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.
Department of Medicine, Division of Pulmonary and Critical Care Medicine, UCLA Lung Cancer Research Program, David Geffen School of Medicine at UCLA, 37-131 Center for Health Sciences, 0833 LeConte Avenue, Los Angeles, CA 90095-1690, USA. sharmasp@ucla.edu
Sherven
S
Sharma
Raj K
RK
Batra
Seok Chul
SC
Yang
Sven
S
Hillinger
Li
L
Zhu
Kimberly
K
Atianzar
Robert M
RM
Strieter
Karen
K
Riedl
Min
M
Huang
Steven M
SM
Dubinett
D002282:Adenocarcinoma, Bronchiolo-Alveolar / Q000276:immunology* / Q000628:therapy*; D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D003713:Dendritic Cells / Q000276:immunology*; D005822:Genetic Vectors; D016219:Immunotherapy, Adoptive; D015851:Interleukin-7 / Q000235:genetics*; D008175:Lung Neoplasms / Q000276:immunology / Q000628:therapy*; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D012074:Remission Induction; D014161:Transduction, Genetic
D015851:Interleukin-7