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

• Published in: Experimental dermatology 2004-06, Vol.13 (6), p.380-390
• Main Authors: Keyser, Johanna, Schultz, Jan, Ladell, Kristin, Elzaouk, Lina, Heinzerling, Lucie, Pavlovic, Jovan, Moelling, Karin
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; cancer immunotherapy; Carcinoma, Lewis Lung - pathology; Carcinoma, Lewis Lung - therapy; CD4-Positive T-Lymphocytes - pathology; CD8-Positive T-Lymphocytes - pathology; Chemokine CXCL10; Chemokines, CXC - genetics; Dermatology; Disease Models, Animal; Genetic Therapy - methods; interferon-induced protein of 10 kDa; interleukin-12; Interleukin-12 - genetics; Killer Cells, Natural - pathology; Lung Neoplasms - pathology; Lung Neoplasms - secondary; Lung Neoplasms - therapy; Medical sciences; melanoma; Melanoma - secondary; Melanoma - therapy; Mice; Mice, Inbred C57BL; Mice, Nude; naked DNA; Plasmids - pharmacology; Skin Neoplasms - pathology; Tumors of the skin and soft tissue. Premalignant lesions
• ISSN: 0906-6705; 1600-0625
• DOI: 10.1111/j.0906-6705.2004.00191.x

:  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.