Prevention of angiogenesis by naked DNA IL-12 gene transfer: angioprevention by immunogene therapy

Morini, M.; Albini, A.; Lorusso, G.; Moelling, K.; Lu, B.; Cilli, M.; Ferrini, S.; Noonan, D.M.
February 2004
Gene Therapy;Feb2004, Vol. 11 Issue 3, p284
Academic Journal
IL-12 is thought to induce a cytokine cascade with antiangiogenic effects mediated by IFN-? and angiostatic CXCR3 chemokine ligands. Naked DNA intramuscular injection of an expression vector plasmid producing IL-12 resulted in significant, well-tolerated elevation of serum IL-12 levels. Injection of the IL-12 plasmid at least 2 days, and up to 20 days, before subcutaneous injection of matrigel with angiogenic factors resulted in strong prevention of angiogenesis in both C57/bl and nude mice. A single injection of the IL-12 plasmid contemporarily with the matrigel or 2 days after resulted in partial, statistically not significant, inhibition. Control plasmid injection did not affect either angiogenesis or angiogenesis inhibition by IL-12 protein in vivo. Angiogenesis inhibition was observed in NK cell-depleted C57/bl and nude mice as well as in IFN-?-/- and CXCR3-/- knockout mice, indicating that NK- and/or T-cell-initiated IFN-?-chemokine cascades were not involved in the angiogenesis inhibition observed in vivo. Finally, IL-12 plasmid DNA gene transfer significantly prevented the growth and vascularization of highly angiogenic KS-Imm Kaposi's sarcoma and TS/A murine mammary carcinoma tumors in nude and/or syngeneic mice. These data suggest that a preventive gene therapy approach using antiangiogenic cytokines can effectively inhibit tumor angiogenesis and KS, representing an example of angioimmunoprevention.Gene Therapy (2004) 11, 284-291. doi:10.1038/sj.gt.3302175


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