IP-10-encoding plasmid DNA therapy exhibits anti-tumor and anti-metastatic efficiency.
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.
Keyser
Johanna
J
Institute of Medical Virology, University of Zurich, Gloriastr., Zurich, Switzerland.
Schultz
Jan
J
Ladell
Kristin
K
Elzaouk
Lina
L
Heinzerling
Lucie
L
Pavlovic
Jovan
J
Moelling
Karin
K
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000473:pathology; D018827:Carcinoma, Lewis Lung / Q000473:pathology / Q000628:therapy; D054357:Chemokine CXCL10; D019743:Chemokines, CXC / Q000235:genetics*; D004195:Disease Models, Animal; D015316:Genetic Therapy / Q000379:methods*; D018664:Interleukin-12 / Q000235:genetics; D007694:Killer Cells, Natural / Q000473:pathology; D008175:Lung Neoplasms / Q000473:pathology / Q000556:secondary* / Q000628:therapy*; D008545:Melanoma / Q000556:secondary* / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D010957:Plasmids / Q000494:pharmacology; D012878:Skin Neoplasms / Q000473:pathology*
D054357:Chemokine CXCL10; D019743:Chemokines, CXC; D018664:Interleukin-12