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Adenovirus‐mediated gene transfer in canine eyes: a preclinical study for gene therapy of human uveal melanoma
Author(s) -
Andrawiss Mariam,
Maron Anne,
Beltran William,
Opolon Paule,
Connault Elizabeth,
Griscelli Frank,
Yeh Patrice,
Perricaudet Michel,
Devauchelle Patrick
Publication year - 2001
Publication title -
the journal of gene medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.689
H-Index - 91
eISSN - 1521-2254
pISSN - 1099-498X
DOI - 10.1002/1521-2254(200105/06)3:3<228::aid-jgm186>3.0.co;2-a
Subject(s) - gene transfer , genetic enhancement , melanoma , gene , medicine , cancer research , virology , biology , genetics
Background Melanomas of the uveal tract are the most common intraocular malignancies in adults, with an incidence of six cases per million adults per year. Enucleation, which may enhance the dissemination of tumour cells into the systemic circulation, is still required for eyes with large tumours. Gene therapy is proposed as a new therapeutic approach for uveal melanoma management. Methods The potential of adenovirus‐mediated gene transfer to normal eyes of two laboratory Beagles and in an iris tumour of a Great Dane were evaluated. Replication‐defective adenoviral vectors (Adβgal) were used to assess the feasibility, efficiency and safety of direct adenoviral delivery to the anterior chamber of normal eyes and to an iris tumour. The expression of angiostatin into the aqueous humour following an adenoviral‐mediated delivery of human angiostatin (AdK3) was also investigated. Results The ciliary body was the area preferentially transduced after adenoviral injection into the anterior chamber. It was also demonstrated that a direct intratumoral injection of a recombinant adenovirus efficiently transduces a canine uveal melanoma. Western blot analysis performed on the aqueous humour revealed that the expression of the angiostatin recombinant protein in the aqueous humour correlated with the dose of AdK3 administered. Lymphocyte infiltrates at the site of AdK3 injection indicated induction of a strong cellular immune response, and humoral immune responses developed in all three dogs. Conclusions The present study involving adenovirus‐mediated gene transfer to dog eyes provides an essential basis for gene therapy treatment of uveal melanoma‐bearing patients. Copyright © 2001 John Wiley & Sons, Ltd.