Gene therapy for preventing the metastasis of intraocular melanoma

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

Research output: Contribution to journalArticle

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)
JournalInvestigative Ophthalmology and Visual Science
Volume37
Issue number3
StatePublished - Feb 15 1996

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Genetic Therapy
Melanoma
Neoplasm Metastasis
Plasminogen Activator Inhibitor 1
Genes
Enzyme-Linked Immunosorbent Assay
Polyomavirus Transforming Antigens
Neoplasms
Plasminogen Activators
Liver
Tumor Cell Line
Cytomegalovirus
Adenoviridae
Nude Mice
Therapeutics
Complementary DNA
Cell Line
Survival
Incidence

ASJC Scopus subject areas

  • Ophthalmology

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Gene therapy for preventing the metastasis of intraocular melanoma. / Niederkorn, J. Y.; Ma, D.; Li, X. Y.; Gerard, R. D.

In: Investigative Ophthalmology and Visual Science, Vol. 37, No. 3, 15.02.1996.

Research output: Contribution to journalArticle

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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.",
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