PARVOVIRUS-BASED ANTICANCER THERAPIES

Contact:

Christiane Dinsart, PhD

Tel. +49 6221 42 49 65
FAX +49 6221 42 49 62
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Some cancers have a desolate prognosis and constitute obvious targets for innovative therapies including virus-based treatments. Candidate oncolytic viruses notably include autonomous parvoviruses of rodent origin (PV). The anticancer potential of these viruses is supported by a set of observations in preclinical models. Yet the mere fact that several PVs were isolated from growing tumours, and the varying sensitivity of transformed human cell cultures to PV infection, indicate that the natural viruses are not always potent enough to override cancer cell proliferation. Nevertheless, the oncotropic nature of PVs together with their low pathogenicity, make them attractive vectors for tumour-directed therapy. Over the last few years, we have designed recombinant vectors (recPV) armed with therapeutic transgenes to reinforce their anti-neoplastic activity and/or to circumvent the resistance of tumour cells to conventional treatments. Hence, recombinant vectors based on H-1PV and MVMp have been designed to deliver immunostimulatory molecules. These immunomodulators, such as cytokines will be secreted from infected cells and induce antitumour effects by activating the immune system.

Since many tumours, in particular brain tumours, are highly vascularised. anti-angiogenic therapies using appropriate recPVs are worth considering. Hence revPVs will also be engineered to deliver anti-angiogenic molecules. They should combine their intrinsic oncolytic activity with the expression of different anti-angiogenic molecules in the vicinity of tumours. The ability to inhibit the tumour growth will be tested using relevant pre-clinical (human) tumour models.
Our goal is thus to provide proof of concept regarding the therapeutic potency of combinatorial treatments consisting of PVs and immunostimulatory and/or anti-angiogenic molecules