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Exp Dermatol. 2004 Jun;13(6):380-90.

IP-10-encoding plasmid DNA therapy exhibits anti-tumor and anti-metastatic efficiency.

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1
Institute of Medical Virology, University of Zurich, Gloriastr., Zurich, Switzerland.

Abstract

We report here that the interferon-induced protein of 10 kDa (IP-10 or CXCL10) elicits strong anti-tumor and anti-metastatic responses in mice when administered by plasmid DNA. Intratumoral but not intramuscular IP-10 DNA inoculation resulted in reduced tumor formation of malignant melanoma (B16F10) and Lewis lung carcinoma (LL/2) in C57BL/6 mice. In addition, plasmid DNA-encoding IP-10 substantially reduced the establishment of metastases when injected systemically by the intramuscular route. In contrast to the primary tumor model, the anti-metastatic effect of DNA-encoding IP-10 was primarily mediated by NK cells. Compared to DNA-encoding interleukin-12 (IL-12), therapy with DNA-encoding IP-10 exhibits lower efficacy against primary melanoma tumors but equivalent efficacy against primary Lewis lung tumors and against B16F10 lung metastasis formation. Co-administration of DNA-encoding IP-10 and IL-12 enhanced the anti-tumor activity of IL-12 in the lung metastasis model but had little effect in the local treatment of established subcutaneous tumors. Interestingly, treatment of nude mice lacking T lymphocytes with DNA-encoding IP-10 or IL-12 still resulted in a pronounced reduction of tumor growth or metastasis formation.

[Indexed for MEDLINE]

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