IMPROVED EFFICACY OF CHEMOTHERAPY BY PARVOVIRUS-MEDIATED SENSITIZATION OF HUMAN TUMOR-CELLS

Increasing resistance of tumour cells towards the cytotoxic action of chemotherapeutic drugs is a major limitation in the treatment of cance r patients. The non-pathogenic human adeno-associated viruses (AAV) ha ve been reported to sensitise HeLa cervical cancer cells to gamma irra diation in vivo and in vitro. To test whether these parvoviruses might render other human tumour cells more sensitive towards chemotherapeut ic drugs, we analysed the effects of AAV type 2 (AAV-2) infection on e stablished cancer cell lines and freshly explanted tumour biopsies tre ated with chemotherapeutic agents (e.g. cisplatin). AAV-2 infection si gnificantly increased the cytotoxic activity of chemotherapeutic drugs compared with uninfected controls. AAV-2 infection without concomitan t chemotherapeutic treatment had no significant effect on viability of the cells. In nude mice, combined application of AAV-2 infection and chemotherapeutic treatment significantly increased the therapeutic act ivity on tumours arising from subcutaneously injected tumour cells com pared with tumours treated by chemotherapeutics only. These results in dicate that AAV-2 infection sensitises human cancer cells towards the cytotoxic action of chemotherapeutic drugs. Copyright (C) 1996 Elsevie r Science Ltd