Interleukin-7 Gene-Modified Dendritic Cells Reduce Pulmonary Tumor Burden in Spontaneous Murine Bronchoalveolar Cell Carcinoma

Sherven Sharma; Raj K. Batra; Seok Chul Yang; Sven Hillinger; L. I. Zhu; Kimberly Calica Atianzar; Robert M. Strieter; Karen Riedl; Min Huang; Steven M. Dubinett

doi:10.1089/104303403322495025

Interleukin-7 Gene-Modified Dendritic Cells Reduce Pulmonary Tumor Burden in Spontaneous Murine Bronchoalveolar Cell Carcinoma

Sherven Sharma, Raj K. Batra, Seok Chul Yang, Sven Hillinger, L. I. Zhu, Kimberly Calica Atianzar, Robert M. Strieter, Karen Riedl, Min Huang, Steven M. Dubinett

Cardiology

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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)-γ and IL-12 as well as an increase in the antiangiogenic chemokines, IFN-γ-inducible protein 10 (IP-10/CXCL10) and monokine induced by IFN-γ (MIG/CXCL9). In contrast, production of the immunosuppressive mediators IL-10, transforming growth factor (TGF)-β, prostaglandin E₂ (PGE₂), 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.

Original language	English (US)
Pages (from-to)	1511-1524
Number of pages	14
Journal	Human Gene Therapy
Volume	14
Issue number	16
DOIs	https://doi.org/10.1089/104303403322495025
State	Published - Nov 1 2003

ASJC Scopus subject areas

Molecular Medicine
Molecular Biology
Genetics

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title = "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)-γ and IL-12 as well as an increase in the antiangiogenic chemokines, IFN-γ-inducible protein 10 (IP-10/CXCL10) and monokine induced by IFN-γ (MIG/CXCL9). In contrast, production of the immunosuppressive mediators IL-10, transforming growth factor (TGF)-β, prostaglandin E2 (PGE2), 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.",

author = "Sherven Sharma and Batra, {Raj K.} and Yang, {Seok Chul} and Sven Hillinger and Zhu, {L. I.} and Atianzar, {Kimberly Calica} and Strieter, {Robert M.} and Karen Riedl and Min Huang and Dubinett, {Steven M.}",

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AU - Sharma, Sherven

AU - Batra, Raj K.

AU - Yang, Seok Chul

AU - Hillinger, Sven

AU - Zhu, L. I.

AU - Atianzar, Kimberly Calica

AU - Strieter, Robert M.

AU - Riedl, Karen

AU - Huang, Min

AU - Dubinett, Steven M.

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N2 - 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)-γ and IL-12 as well as an increase in the antiangiogenic chemokines, IFN-γ-inducible protein 10 (IP-10/CXCL10) and monokine induced by IFN-γ (MIG/CXCL9). In contrast, production of the immunosuppressive mediators IL-10, transforming growth factor (TGF)-β, prostaglandin E2 (PGE2), 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.

AB - 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)-γ and IL-12 as well as an increase in the antiangiogenic chemokines, IFN-γ-inducible protein 10 (IP-10/CXCL10) and monokine induced by IFN-γ (MIG/CXCL9). In contrast, production of the immunosuppressive mediators IL-10, transforming growth factor (TGF)-β, prostaglandin E2 (PGE2), 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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Interleukin-7 Gene-Modified Dendritic Cells Reduce Pulmonary Tumor Burden in Spontaneous Murine Bronchoalveolar Cell Carcinoma

Abstract

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