RGD Reference Report - Monocyte chemoattractant protein-1 gene delivery enhances antitumor effects of herpes simplex virus thymidine kinase/ganciclovir system in a model of colon cancer.

General

Monocyte chemoattractant protein-1 gene delivery enhances antitumor effects of herpes simplex virus thymidine kinase/ganciclovir system in a model of colon cancer.
Authors:	Kagaya, T Nakamoto, Y Sakai, Y Tsuchiyama, T Yagita, H Mukaida, N Kaneko, S
Citation:	Kagaya T, etal., Cancer Gene Ther. 2006 Apr;13(4):357-66.
RGD ID:	8548881
Pubmed:	PMID:16224495 (View Abstract at PubMed)
DOI:	DOI:10.1038/sj.cgt.7700908 (Journal Full-text)
Suicide gene therapy using the herpes simplex virus thymidine kinase/ganciclovir (HSV-tk/GCV) system is a well-characterized tool for cancer gene therapy; however, it does not yet exhibit sufficient efficacy to cure patients of malignancies. We have reported that adenovirally delivered monocyte chemoattractant protein (MCP)-1 augmented the antitumor effects of the HSV-tk/GCV system in an athymic nude mouse model. The current study, which uses an immunocompetent mouse model of colon cancer, was designed to evaluate the antitumor effects of MCP-1 gene delivery in conjunction with this suicide gene therapy system. Subcutaneous tumor foci were directly transduced with both recombinant adenoviruses (rAds) expressing an HSV-tk gene and either of the MCP-1, CD80 and LacZ genes, followed by GCV administration. The growth of tumors was markedly suppressed by codelivery of HSV-tk and MCP-1 genes, which was exclusively associated with the recruitment of monocytes/macrophages, T helper 1 (Th1) cytokine gene expression and cytotoxic activity of the splenocytes. Furthermore, the antitumor effects were more efficient than that obtained by the combination of HSV-tk and CD80 genes. These results suggest an immunomodulatory effect of MCP-1 in the context of suicide gene therapy of colon cancer via orchestration of innate and acquired immune responses.

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Term	Qualifier	Evidence	With	Reference	Notes	Source	Original Reference(s)
Colonic Neoplasms	treatment	IDA		8548881	human gene in mouse model	RGD
Colonic Neoplasms	treatment	ISO	CCL2 (Homo sapiens)	8548881; 8548881	human gene in mouse model	RGD

Objects Annotated

Genes (Rattus norvegicus)

Ccl2 (C-C motif chemokine ligand 2)

Genes (Mus musculus)

Ccl2 (C-C motif chemokine ligand 2)

Genes (Homo sapiens)

CCL2 (C-C motif chemokine ligand 2)

Objects referenced in this article

Gene	CCL13	C-C motif chemokine ligand 13	Homo sapiens

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Monocyte chemoattractant protein-1 gene delivery enhances antitumor effects of herpes simplex virus thymidine kinase/ganciclovir system in a model of colon cancer.