1. ¹Department of Applied Tumour Virology, German Cancer Research Centre, Heidelberg, Germany
2. ²Clinical Cooperation Unit Nuclear Medicine, Department of Nuclear Medicine, University of Heidelberg, Heidelberg, Germany

Correspondence: Dr JA Kleinschmidt, Department of Applied Tumour Virology, German Cancer Research Centre, Im Neuenheimer Feld 242, Heidelberg 69120, Germany. E-mail: j.kleinschmidt@dkfz.de

Received 28 July 2007; Revised 15 November 2007; Accepted 25 November 2007; Published online 18 January 2008.

Abstract

Autonomous parvoviruses possess an intrinsic oncotropism based on viral genetic elements controlling gene expression and genome replication. We constructed a hybrid vector consisting of the H1 parvovirus-derived expression cassette comprising the p4 promoter, the ns1 gene and the p38 promoter flanked by the adeno-associated viruses 2 (AAV2) inverted terminal repeats and packaged into AAV2 capsids. Gene transduction using this vector could be stimulated by coinfection with adenovirus, by irradiation or treatment with genotoxic agents, similar to standard AAV2 vectors. However, the latter were in most cases less efficient in gene transduction than the hybrid vector. With the new vector, tumor cell-selective increase in transgene expression was observed in pairs of transformed and non-transformed cells, leading to selective killing of the transformed cells after expression of a prodrug-converting enzyme. Preferential gene expression in tumor versus normal liver tissue was also observed in vivo in a syngeneic rat model. Comparative transduction of a panel of different tumor cell lines with the H1 and the H1/AAV hybrid vector showed a preference of each vector for distinct cell types, probably reflecting the dependence of the viral tropism on capsid determinants.