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Article Title:
==============

Will "Linked Recognition" Lead to a Cancer Vaccine?

Article Description:
====================

Dr. Lorne Tyrrell pioneered lamivudine as the standard treatment
for hepatitis B virus (HBV). Now a success, he observed the
drug's shortcomings. Now CEO of ViRexx Medical, Tyrrell hopes
his latest development, Chimigen, will offer new hope for HBV,
other infectious diseases, and cancer.


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===============================

1080 Words; formatted to 65 Characters per Line
Distribution Date and Time: 2006-06-01 11:24:00

Written By: James Finch
Copyright: 2006
Contact Email: mailto:article-info@...

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Will "Linked Recognition" Lead to a Cancer Vaccine?
Copyright © 2006 StockInterview.com
Written by: James Finch
Stock Interview
http://www.stockinterview.com



A SCIENTIST'S 20-YEAR UNFINISHED JOURNEY TO TREAT HBV MAY OPEN
THE DOOR TO A NEW CLASS OF FLEXIBLE VACCINES

While preparing a lecture in biochemistry and virology for his
graduate students at the University of Alberta in the early
1980s, Dr. Lorne Tyrrell ran across a study just published in the
medical journal, Cell. The research by William Mason and Jesse
Summers, entitled "Replication of Hepatitis B," discussed their
study of the hepatitis B virus in infected duck liver.

After studying their duck model theory, Tyrrell speculated if the
hepatitis B virus (HBV) might be susceptible to antiviral agents,
and consulted with a colleague, who specialized in nucleoside
chemistry. Both medical professors became excited about the
possibility of inhibiting the HBV virus with nucleoside
analogues. Thus began the infectious disease specialist's first
leg of a journey, which led to the use of lamivudine as a therapy
for chronic HBV infections.

More than 350 million people across the world, especially in
Asia, now had new hope, some for their lifelong infections
contracted vertically at birth from their mothers. In 2003, the
Center for Disease Control estimated 73,000 Americans were
infected with HBV, and about 5,000 die each year from sickness
caused by HBV. It is reportedly 100 times more contagious than
the AIDS virus. Many in North America, who had been infected with
the virus from sexual transmission or intravenous drug use, were
offered a potentially life-saving therapy.

Licensed in 1998, lamivudine is now used in 120 countries as a
standard therapy for chronic HBV carriers. The compound is also
used in combination with other drugs, such as protease
inhibitors, for HIV therapy. Development rights were licensed to
Glaxo Wellcome in 1990, which is now sold under the brand name
Epivir®. For his pioneering efforts in developing the antiviral
agent, Dr. Tyrrell was awarded the gold medal by the Canadian
Liver Foundation and the Canadian Association for the Study of
Liver in 2000. In 2005, he won the prestigious EnCana Principal
Award for his development of the first effective oral medication
for Hepatitis B.


HIS UNANSWERED QUESTIONS LAUNCHED A NEW HBV INVESTIGATION

Despite the awards and recognition, questions remained for Dr.
Tyrrell about the shortcomings of lamivudine. He was troubled
that some viruses would develop resistance to the compound. "I
was disappointed the sustained viral response was not complete,"
Tyrrell told us. In April 2003, the Journal of Antimicrobial
Chemotherapy published a study in Japan showing, "long-term
(lamivudine) therapy is associated with increased emergence of
lamivudine-resistant strains of HBV." Researchers concluded in
this study, "The therapeutic challenge to effectively treat
chronic HBV infection continues."

Having screened lamivudine for use in Hepatitis B at Glaxo's
research lab at the University of Alberta, Dr. Tyrrell was able
to observe the immune response of various HBV patients. "What
really got me interested in doing more work in this area was that
we noticed patients, who have an immune response to the virus and
take lamivudine, will have a better sustained response rate,"
Tyrrell explained. "A patient with elevated liver transaminases
taking lamivudine had a higher probability of a sustained viral
response," Tyrrell said with excitement in his voice. "In a
patient with normal liver enzymes, who gets lamivudine, the virus
will go down, but as soon as you stop the therapy, the virus
comes right back up." He told us the sustained viral response is
only about two to three percent. Only about 30 percent remain
free of the virus, about one year after patients have stopped
taking lamivudine.

"How do you break tolerance?" Tyrrell asked himself, hoping to
develop a way to stimulate an immune response. All of the
patients, he had observed, seemed to be tolerant of the hepatitis
B virus. He pondered the dilemma, "Was there some way to break
tolerance to hepatitis B by stimulating the immune response?"
Tyrrell studied what others were attempting and wasn't satisfied
with the approaches others were taking to stimulate immune
response. His ViRexx Medical research team brainstormed about
different ways to target the antigen into the dendritic cells.

"That's where we came in with the Chimigen™ technology,"
Tyrrell said. "The dendritic cells have receptors on their
surface that will bind the Fc portion of an antibody." He
pointed out a key feature of the Chimigen™ platform, "We used
the Fc portion of a murine (mouse) antibody to hook onto our
hepatitis B antigens. This would direct the viral antigens into
dendritic cells in vivo." Because the dendritic cells are the
sentries of the immune system, they guard what comes in.
Recognizing a 'foreign situation' in the murine antibody, it
treats the whole molecule including the virus antigen as foreign.



LINK RECOGNITION MAY HOLD THE KEY

Dr. Rajan George, ViRexx Medical's vice president of research
and development, told us, "The dendritic cells chop up this
protein into small pieces called peptides, also known as
epitopes. The dendritic cells have a system where they put the
T-cell epitope on another protein, MHC Class I, and bring it to
the surface of the dendritic cell. They are presented as a
complex on the surface of the dendritic cell to attract the
T-cells." When the T-cells arrive to inspect the foreign entity,
the cytotoxic T-cells are activated. Then, they begin attacking
and killing the virus-infected cells.

Research at Tokyo's Cancer Institute Hospital, published in 1987
in Nippon Sanka Fujinka Gakkai Zasshi, suggested a feasibility of
linked recognition of a virus antigen as a helper in tumor
immunity with a target antigen. In the case of ViRexx Medical,
Tyrrell's team has created a new molecule, called "chimigen."
The term is shorthand for a chimeric antigen, meaning it is an
antigen created from two different sources, part virus and part
murine monoclonal antibody.

Dr. Tyrrell's work at ViRexx Medical with Dr. George suggested
the linked-recognition theory might be the key to breaking
tolerance. Dr. George emphasized, "The new 'chimigen'
stimulates an immune response to the antigen as well as the viral
antigen. This is very important because the virus antigen was
previously being ignored." That brings us back to why lamivudine
had limited success. The immune systems of some HBV carriers
failed to recognize the viral infection as a threat to the body.
Tyrell's ViRexx Medical research team hopes the body's immune
system sees the threat, thus stimulating the immune system, and
breaking tolerance. It appears Dr. Tyrell may soon find out
whether or not the questions he asked will bring the answers he
hoped for.

END OF PART ONE





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To read Part 2 of this interview, please
visit http://www.stockinterview.com
James Finch contributes to StockInterview.com
and other publications. Write to James Finch
at: jfinch@...



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