Visit our Expo - Redox and Inflammation signaling 2012

New steps toward the use of parvovirus H1 as a therapeutic anti-cancer drug
D.Stéhelin, N.Martin, G.Muharram, A.Bègue, C.Lagrou, A-C.Flourens A.Roussel,
I.Loison.
CNRS-UMR 8526. Institute of Biology of Lille, 1 rue Calmette-BP 447, 59021 Lille
Cedex. dominique.stehelin@ibl.fr
Recent emphasis (Int J Oncol. 4, 2005, 901; Nature Medicine 8, 2000, 862 ; Nature
Biotechnology 18, 2000, 723) has brought into focus the intriguing property of some viruses
that are able to quite selectively destroy many types of tumour cells. Our laboratory has been
studying such a virus, namely parvovirus H1, which opportunistically infects the human
population, but apparently without any known pathology in adults.
Parvovirus H1 exhibits quite remarkable features in cell cultures: 1)It infects preferentially
many types of human tumour cells. 2)The cells replicating the virus are rapidly killed (ex vivo
in c.a. 3-5 days), releasing viral progeny. 3)The new virus readily infects the neighbouring
tumour cells in a recurrent fashion
In vivo experiments showed that SCID mice injected with human tumour cell-lines (i.e.
HeLa) develop tumours and rapidly die, unless they are injected with Parvovirus H1, in which
case the tumours regress, then disappear definitely, preventing the animal from dying.
A small Phase1 clinical trial carried on with T.Tursz at the IGR Hospital in Villejuif, in
collaboration with J.Rommelaere (Heidelberg), gave encouraging results: 1)High doses of
parvovirus could be injected, apparently without hampering essential life parameters.
2)Repeated injections could be applied, without observing deleterious high antibody levels.
3)A systemic spread of the virus was observed, where the virus could reach distal metastases
which sustained its replication. 4)The virus disappeared following the last injection.
These promising results encouraged us to further investigate the mechanism by which the
virus is able to selectively destroy tumour cells, and to decipher why so many different types
of tumour cells are efficient targets for parvoviral mediated oncolysis. We will also present
recent achievements concerning the preparation of purified parvovirus grown on cells without
any animal fraction, and our preliminary predictive test to determine if fresh human tumours
are responsive to parvoviral kelling.
We recently obtained an important research grant that should allow us to progress toward a
potential use of this virus in anticancer therapy.
References:
FAISST, S., D.GUITTARD, A.BENNER, Y.Y.CESBRON, J.R.SCHLEHOFER,
J.ROMMELAERE and
T.DUPRESSOIR
Dose-dependent regression of HeLa cell-derived tumours in scid mice after parvovirus
H-1 infection
International Journal of Cancer (1998) 75 : 584-589
DUTHEIL, N., F.SHI, T.DUPRESSOIR and R.M.LINDEN
Adeno-associated virus site-specifically integrates into a muscle-specific DNA region
Proc. Natl. Acad. Sci. USA (2000) 97 : 4862-4866
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