Reduction of liver metastasis of intraocular melanoma by interferon-beta gene transfer
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Updated: Sep 23, 2026
Isolated Hepatic Perfusion as a Treatment for Liver Metastases of Uveal Melanoma
Published on: January 25, 2015
Hassan Alizadeh1, Kevin Howard, Jessee Mellon
1Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9057, USA.
Purpose:
This study determined whether adenovirus-mediated transfer of the murine interferon-beta (AdCMVIFN-beta) gene protects against liver metastases arising from intraocular melanomas in mice.
Methods:
A replication-deficient adenovirus vector (AdCMVIFN-beta) was used for the in vivo transfer of the murine IFN-beta gene into intraocular melanoma-bearing mice. AdCMVIFN-beta was injected either intravenously or directly into the intraocular melanomas. The effect of gene transfer on liver metastases was ascertained by histopathologic analysis of the livers and by measuring serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), which are two enzymes associated with liver metastases in patients with uveal melanoma.
Results:
Mice treated with two intratumoral injections of AdCMVIFN-beta had a 68% reduction in metastatic liver lesions (P = 0.016) and a 51% reduction in liver enzyme levels compared with control mice (P = 0.02). However, the antimetastatic effect of AdCMVIFN-beta was not directly attributable to the adenovirus vector or virus-mediated cytolysis of tumor cells. Intravenous treatment with AdCMVIFN-beta resulted in an 86% reduction in the number of metastatic foci in the liver (P = 0.014) and a 61% reduction of serum AST levels compared with mice treated with AdCMVLacZ (P = 0.015). AdCMVIFN-beta treatment produced a sharp increase in the NK cell activity that was demonstrable in vivo and in vivo. In vivo depletion of NK cells by anti-asialo GM1 antibody abrogated the antimetastatic effects of AdCMVIFN-beta.
Conclusions:
The results support the feasibility of activation of NK cell function through gene transfer as one possible therapeutic strategy for reducing hepatic metastases of uveal melanomas.
Insights
Adenovirus-mediated transfer of the murine interferon-beta gene significantly reduced liver metastases from intraocular melanomas in mice. This therapeutic strategy activates natural killer (NK) cell function, offering a potential approach for treating uveal melanoma hepatic metastases.
Area of Science:
- Ophthalmology
- Oncology
- Gene Therapy
Background:
- Intraocular melanomas can metastasize to the liver, posing a significant clinical challenge.
- Current treatments for uveal melanoma hepatic metastases are limited, necessitating novel therapeutic strategies.
Purpose of the Study:
- To determine if adenovirus-mediated transfer of the murine interferon-beta (AdCMVIFN-beta) gene can prevent liver metastases from intraocular melanomas in a mouse model.
- To investigate the mechanism by which AdCMVIFN-beta exerts its antimetastatic effects.
Main Methods:
- Replication-deficient adenovirus vector (AdCMVIFN-beta) used for in vivo gene transfer into intraocular melanoma-bearing mice.
- Intravenous or intratumoral injections of AdCMVIFN-beta administered.
- Liver metastases assessed via histopathology and serum liver enzyme levels (AST, ALT).
- Natural killer (NK) cell activity evaluated in vivo and in vitro; NK cell depletion used to test mechanism.
Main Results:
- Two intratumoral AdCMVIFN-beta injections reduced liver lesions by 68% (P=0.016) and liver enzymes by 51% (P=0.02).
- Intravenous AdCMVIFN-beta reduced liver metastases by 86% (P=0.014) and serum AST by 61% (P=0.015).
- AdCMVIFN-beta treatment significantly increased NK cell activity, and NK cell depletion abrogated the antimetastatic effect.
Conclusions:
- Adenovirus-mediated interferon-beta gene transfer is a feasible strategy for reducing hepatic metastases of intraocular melanomas.
- Activation of NK cell function is a key mechanism underlying the antimetastatic efficacy of this gene therapy.
- This approach holds promise as a potential therapeutic strategy for uveal melanoma patients with liver metastases.
