Combretastatin A-1 phosphate potentiates the antitumor activity of carboplatin and paclitaxel in a severe combined immunodeficiency disease (SCID) mouse model of human ovarian carcinoma.

In search for new therapeutic modalities to target epithelial ovarian carcinomas, we investigated the effect of the antiangiogenic drug combretastatin A-1 phosphate (CA1P) as a single treatment or in combination with established therapy, ie, carboplatin and paclitaxel. Five different human epithelial ovarian carcinoma cell lines were inoculated subcutaneously into FOX CHASE CB-77 severe combined immunodeficiency disease (SCID) mice. When tumors reached a volume of approximately 100 mm(3), the treatment was initiated. All drugs were given intraperitoneally at weekly doses. CA1P was more effective as an antitumor agent than combretastatin A-4 phosphate as a single-drug treatment or in combination with carboplatin and paclitaxel. CA1P had a strong tumor outgrowth inhibiting effect on four out of five tumors included in this study. Comparing animals receiving CA1P with animals receiving a combination of carboplatin and paclitaxel, CA1P was more effective on two out of three tested tumors, whereas carboplatin and paclitaxel were more effective on one out of three of the tumors. We show that treatment of human ovarian carcinomas with CA1P in the SCID mouse model results in a strong antitumor effect both as a single-drug treatment and as an enhancement of the therapeutic effect in a combination treatment protocol with carboplatin and paclitaxel.

Efficient transduction of neurons using Ross River glycoprotein-pseudotyped lentiviral vectors.

Lentiviral vectors are promising tools for CNS gene transfer since they efficiently transduce the cells of the nervous system in vivo. In this study, we have investigated the transduction efficiency of lentiviral vectors pseudotyped with Ross River virus glycoprotein (RRV-G) (RRV-G-pseudotyped lentiviral vectors (RRV-LV)). The RRV is an alphavirus with an extremely broad host range, including the cells of the central nervous system. Previous studies have shown that lentiviral vectors can be efficiently pseudotyped with this envelope protein and have demonstrated promising features of such vectors, including the possibility to establish stable producer cell lines. After injection of RRV-LV expressing green fluorescent protein into different structures in the rat brain we found efficient transduction of both neurons and glial cells. By using two cell-type-specific promoters, neuron-specific enolase and human glial fibrillary acidic protein, we demonstrated cell-specific transgene expression in the desired cell type. Ross River virus glycoprotein-pseudotyped lentiviral vectors also transduced human neural progenitor cells in vitro, showing that receptors for the RRV-G are present on human neural cells.