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.
Sharma
Sherven
S
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
Batra
Raj K
RK
Yang
Seok Chul
SC
Hillinger
Sven
S
Zhu
Li
L
Atianzar
Kimberly
K
Strieter
Robert M
RM
Riedl
Karen
K
Huang
Min
M
Dubinett
Steven M
SM
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