Gene therapy for preventing the metastasis of intraocular melanoma

J. Y. Niederkorn, D. Ma, X. Y. Li, R. D. Gerard

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose. To evaluate gene transfer for preventing the metastasis of intraocular melanoma in a mouse model. Methods. Human plasminogen activator inhibitor-1 (PAI-1) gene, under a cytomegalovirus promoter, was incorporated into a replication-defective recombinant adenovirus vector (AdCMVPAI-1). A human uveal melanoma cell line (OCM1) and a murine uveal tumor cell line (99E1) were transplanted intracamerally (IC) into nude mice. Gene transfer was accomplished by inoculation of 5×107 plaque forming units into the tumors. Liver metastases were evaluated by histopathology and an enzyme linked immunosorbent assay (ELISA) which detects SV40 T antigen present in the murine 99E1 tumor. Results. AdCMVPAI-1 treatment reduced OCM1 metastases from a 61% (14/23) incidence in untreated mice to 33% (6/18) in AdCMVPAI-1 treated hosts. Treatment with AdCMVPAI-1 also prolonged host survival:100% (10/10) of the untreated hosts died with a mean survival time [MST] of 65 days compared to 70% death (MST = 80 days) in AdCMVPAI-1 treated hosts. An exquisitely sensitive ELISA for quantifying liver metastases indicated that AdCMVPAI-1 treatment reduced the metastatic tumor mass by 78% compared to untreated controls. Conclusion. Disruption of plasminogen activator function of intraocular melanomas via gene transfer of PAI-1 cDNA significantly inhibits spontaneous metastasis of intraocular melanomas and may hold promise for use in humans.

Original languageEnglish (US)
Pages (from-to)S1114
JournalInvestigative Ophthalmology and Visual Science
Volume37
Issue number3
StatePublished - Feb 15 1996

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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