Could Virexx Medical’s 'Linked Recognition' Lead To Cancer Vaccine ?
By Julie Ickes
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
About the Author: To read Part 2 of this interview, please
visit http://www.stockinterview.com James Finch contributes to
http://StockInterview.com and other publications. Write to
James Finch at jfinch@stockinterview.com
Source: http://www.isnare.com
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