Combination of oncolytic virus and chemo deals deadly cancers a knockout punch

From

Dealing deadly cancers a knockout punch
<http://www.eurekalert.org/pub_releases/2007-05/obi-ddc050907.php>:

"New scientific evidence is helping to build a compelling
case for oncolytic viruses as a first-line and adjunctive
treatment for many cancers.

Reovirus, a non-pathogenic virus under development at
Calgary, Alberta-based Oncolytics Biotech, has shown powerful
anti-cancer activity against cultured tumor cells, in animal
models, and in human clinical trials. Oncolytics' proprietary
reovirus formulation, Reolysin®, is active against numerous
cancers, including intractable sarcomas and melanomas.

Recent studies also indicate that Reolysin works
synergistically with standard anti-cancer drugs, providing
significantly stronger responses than either agent alone.

In addition, other studies completed in the past year have
shown Reolysin has the ability to prime patients' immune
systems against their particular cancer, leading to
additional cancer cell killing. It is through this second
"inflammatory" mechanism that researchers hope Reolysin will
bring about long-term remissions of once-untreatable cancers.

At the Fourth International Conference on Oncolytic Viruses
as Cancer Therapeutics in March 2007 in Scottsdale, Arizona,
several presentations focused on reovirus efficacy alone or
in combination with standard chemotherapies.

In one study, investigators examined the tumor-killing
ability of reovirus plus cisplatin, a standard chemotherapy
agent, in a mouse melanoma model that included both cultured
cells and live animals. The results of the preclinical study
showed that the combination of reovirus and cisplatin was
significantly more effective than cisplatin or reovirus alone
at killing melanoma cancer cells in a mouse model. The
investigators intend to explore the mechanism of this
promising synergistic action in further detail in future
preclinical work.

Another presentation at the Arizona conference reported on
the use of Reolysin plus the cancer drug cyclophosphamide in
an animal model of melanoma. When treated with both agents,
test animals experienced enhanced tumor regression compared
with either agent alone, and without additional toxicity.
Oncolytics has permission from the U.K. regulatory
authorities to test Reolysin in three separate human trials
in combination with the cancer drugs gemcitabine,
paclitaxel/carboplatin and docetaxel.

Perhaps the most exciting findings of Reolysin combination
therapy were reported at the American Association for Cancer
Research Annual Meeting in April, 2007. In mice transplanted
with a human colon cancer, Reolysin plus gemcitabine
completely eradicated the tumors in four of five test
animals. It is rare to see the virtual elimination of tumours
as well as the long-lasting therapeutic effect that was
observed in this study.

"Combination therapy results for reovirus in animals are
particularly encouraging because they suggest that Reolysin
can improve the anti-tumor activity of standard chemotherapy
agents in advanced cancer patients without causing additional
toxicity," said Dr. Karl Mettinger, Chief Medical Officer of
Oncolytics.

Physicians often prefer to treat cancer with multiple agents,
but toxicity limits these approaches. Since reovirus
typically is not pathogenic in humans nor associated with
severe toxicity in clinical studies, its co-administration is
not expected to increase a treatment's overall toxicity.

Dual Mechanism

Reovirus works by entering and replicating within cancer
cells containing an activated ras pathway, a mutation present
in about two-thirds of all human cancers. Reovirus enters a
cancer cell, makes thousands of copies of itself, and then
causes the cell to burst, which releases viruses that infect
and kill adjacent cancer cells. Normal cells are not harmed.

In addition to killing cancer cells directly, reovirus is
believed to activate an anti-tumor immune response through
the body's natural killer cells and T cells. Through this
mechanism, which persists for weeks or months, the body
continues to fight off cancer long after the virus clears
from the body.

Future directions

On April 11, 2007, Oncolytics announced it had initiated a
Phase II trial to evaluate intravenous administration of
Reolysin in patients with sarcomas that have metastasized to
the lung. For patients with deadly soft tissue sarcoma, the
lungs are the most common site of metastatic disease. To
date, surgery has been the only effective therapy for
metastatic sarcoma.

The multi-center, Phase II study follows successful
completion of systemic administration trials with Reolysin in
the U.K. and the U.S. This will be the second of several
Phase II trials Oncolytics plans for 2007. The Company also
has a collaborative agreement with the U.S. National Cancer
Institute to conduct multiple clinical trials with Reolysin
which are expected to begin in 2007, including a Phase II
melanoma trial and a Phase I/II ovarian cancer trial.

"It is hoped that the trials will clearly show that Reolysin
alone or in combination with either radiation or chemotherapy
can stop or reverse the growth of advanced cancers without
adding harmful side effects," said Dr. Mettinger."


--
Matti Narkia
.

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