A recombinant Newcastle disease virus kills all kinds of
prostate cancer cells, including hormone resistant cells, but leaves normal
cells unscathed, according to a paper published online ahead of print in the
Journal of Virology.
A treatment for
prostate cancer based on this virus would avoid the adverse side effects
typically associated with hormonal treatment for prostate cancer, as well as
those associated with cancer chemotherapies generally, says corresponding
author Subbiah Elankumaran of Virginia Polytechnic Institute, Blacksburg. The
modified virus is now ready to be tested in preclinical animal models, and
possibly in phase I human clinical trials.
Virus no danger to
humans
Newcastle disease
virus kills chickens, but does not harm humans. It is an oncolytic virus that
hones in on tumours, and has shown promising results in a number of human
clinical trials for various forms of cancer. However, successful treatments
have required multiple injections of large quantities of virus, because in such
trials the virus probably failed to reach solid tumours in sufficient
quantities, and spread poorly within the tumours.
The researchers
addressed this problem by modifying the virus's fusion protein. Fusion protein
fuses the virus envelope to the cell membrane, enabling the virus to enter the
host cell. These proteins are activated by being cleaved by any of a number of
different cellular proteases. They modified the fusion protein in their
construct such that it can be cleaved only by prostate specific antigen (which
is a protease). That minimises off-target losses, because these
"retargeted" viruses interact only with prostate cancer cells, thus
reducing the amount of virus needed for treatment.
Retargeted Newcastle
disease virus has major potential advantages over other cancer therapies, says
Elankumaran. First, its specificity for prostate cancer cells means it would
not attack normal cells, thereby avoiding the various unpleasant side effects
of conventional chemotherapies. In previous clinical trials, even with
extremely large doses of naturally occurring strains, "only mild flu-like
symptoms were seen in cancer patients," says Elankumaran.
Second, it would provide a new treatment for
hormone-refractory patients, without the side effects of testosterone suppression
that result from hormonal treatments.
About one man in six will be diagnosed with prostate cancer,
and one in 36 will die of this disease. Men whose prostate cancer becomes
refractory to hormone treatment have a median survival of about 40 months if
they have bone metastases, and 68 months if they do not have bone metast
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