Inhibition of a vascular ocular tumor growth by IL-12 gene transfer

Adriana Albini, Gianfranco Fassina, Massimo Nicolò, Raffaella Dell'Eva, Roberta Vené, Rosaria Cammarota, Massimo Barberis, Douglas M. Noonan

Research output: Contribution to journalArticlepeer-review

Abstract

Ocular tumors such as retinoblastoma and uveal melanoma have devastating effects on vision. Patients with uveal melanoma also have low 5-year survival rates, thus new therapeutic modalities are necessary. As both retinoblastoma and uveal melanoma are highly vascular, we tested application of a gene transduction approach with a potent TH1 cytokine also endowed with strong anti-angiogenic activity, Interleukin-12 (IL-12). Gene transfer into murine 99E1 uveal melanoma-like cells, while having no effects on growth in vitro, essentially blocked subcutaneous tumor growth in vivo without evident signs of toxicity. Orthotopic intraocular injection resulted in invasive tumors that destroyed ocular architecture by the control cells while the IL-12 transduced cells rarely formed tumors. Histological analysis revealed highly invasive and angiogenic tumor growth in the controls and poorly vascularized tumors in the presence of IL-12. The tumor repression effect could be reproduced by a systemic anti-angiogenic effect, where controlateral injection of IL-12 expressing cells strongly repressed growth in tumors formed by parental 99E1 cells. This was associated with significantly lowered tumor vessel densities, a trend toward lower VEGF levels in the lesion, and significantly decreased NK cells in the parental tumors exposed to systemic IL-12. Taken together, our data suggest that IL-12 gene transfer can provide anti-angiogenic effects without toxicity and may be particularly suited for therapy of vascularized ocular tumors.

Original languageEnglish
Pages (from-to)485-493
Number of pages9
JournalClinical & Experimental Metastasis
Volume24
Issue number7
DOIs
Publication statusPublished - Nov 2007

Keywords

  • Anti-angiogenesis
  • Gene transfer
  • IL-12
  • Ocular tumors
  • Rare diseases
  • Retinoblastoma
  • Uveal melanoma

ASJC Scopus subject areas

  • Cancer Research

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