1. ¹Institute of Molecular Biology, University of Zürich, Zürich, Switzerland
2. ²Department of Dermatology, University Hospital, Zürich, Switzerland
3. ³Institute of Zoology, University of Zürich, Zürich, Switzerland

Correspondence: Dr S Hemmi, Institute of Molecular Biology Zürich, Winterthurerstr. 190, CH-8057 Zürich, Switzerland

Received 16 July 2002; Accepted 22 October 2002.

Abstract

To generate a replication-competent adenovirus (Ad) with specificity for melanoma, we constructed a tissue-specific promoter restricting E1A expression to melanoma cells. The combination of four copies of a mouse tyrosinase enhancer element (TE) fused to the human tyrosinase promoter (TP) yielded up to 2000-fold higher luciferase reporter activity in tyrosinase-expressing melanoma cells than in nonmelanoma cells. Insertion of the composite TETP construct upstream of the E1A gene was combined with deleting as far as possible the intertwined endogenous Ad enhancer/promoter (EP). The resulting AdEP–TETP vector, also deleted for the E3 region, was found to replicate in tyrosinase-positive melanoma cells, such as SK-Mel23 as efficiently as wild-type Ad5, but at a more than 50-fold reduced level in nonmelanoma tumour cells and primary human cells. Injection of AdEP–TETP into xenotransplanted melanomas, but not into HeLa-derived tumours led to long-lasting tumour regression in nude mice. This AdEP–TETP virus might be useful for the treatment of accessible lesions in advanced melanoma patients.