| While preparing a lecture in biochemistry
| |
| | liver enzymes, who gets lamivudine, the
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| and virology for his graduate students at
| |
| | virus will go down, but as soon as you
|
| the University of Alberta in the early
| |
| | stop the therapy, the virus comes right
|
| 1980s, Dr. Lorne Tyrrell ran across a
| |
| | back up." He told us the sustained viral
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| study just published in the medical
| |
| | response is only about two to three
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| journal, Cell. The research by William
| |
| | percent. Only about 30 percent remain
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| Mason and Jesse Summers, entitled
| |
| | free of the virus, about one year after
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| "Replication of Hepatitis B," discussed
| |
| | patients have stopped taking lamivudine.
|
| their study of the hepatitis B virus in
| |
| | "How do you break tolerance?" Tyrrell
|
| infected duck liver.
| |
| | asked himself, hoping to develop a way to
|
| A SCIENTIST'S 20-YEAR UNFINISHED JOURNEY
| |
| | stimulate an immune response. All of the
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| TO TREAT HBV MAY OPEN THE DOOR TO A NEW
| |
| | patients, he had observed, seemed to be
|
| CLASS OF FLEXIBLE VACCINES
| |
| | tolerant of the hepatitis B virus. He
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| After studying their duck model theory,
| |
| | pondered the dilemma, "Was there some way
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| Tyrrell speculated if the hepatitis B
| |
| | to break tolerance to hepatitis B by
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| virus (HBV) might be susceptible to
| |
| | stimulating the immune response?" Tyrrell
|
| antiviral agents, and consulted with a
| |
| | studied what others were attempting and
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| colleague, who specialized in nucleoside
| |
| | wasn't satisfied with the approaches
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| chemistry. Both medical professors became
| |
| | others were taking to stimulate immune
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| excited about the possibility of
| |
| | response. His ViRexx Medical research
|
| inhibiting the HBV virus with nucleoside
| |
| | team brainstormed about different ways to
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| analogues. Thus began the infectious
| |
| | target the antigen into the dendritic
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| disease specialist's first leg of a
| |
| | cells.
|
| journey, which led to the use of
| |
| | "That's where we came in with the
|
| lamivudine as a therapy for chronic HBV
| |
| | Chimigen⢠technology," Tyrrell said.
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| infections.
| |
| | "The dendritic cells have receptors on
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| More than 350 million people across the
| |
| | their surface that will bind the Fc
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| world, especially in Asia, now had new
| |
| | portion of an antibody." He pointed out a
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| hope, some for their lifelong infections
| |
| | key feature of the Chimigenâ¢
|
| contracted vertically at birth from their
| |
| | platform, "We used the Fc portion of a
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| mothers. In 2003, the Center for Disease
| |
| | murine (mouse) antibody to hook onto our
|
| Control estimated 73,000 Americans were
| |
| | hepatitis B antigens. This would direct
|
| infected with HBV, and about 5,000 die
| |
| | the viral antigens into dendritic cells
|
| each year from sickness caused by HBV. It
| |
| | in vivo." Because the dendritic cells are
|
| is reportedly 100 times more contagious
| |
| | the sentries of the immune system, they
|
| than the AIDS virus. Many in North
| |
| | guard what comes in. Recognizing a
|
| America, who had been infected with the
| |
| | 'foreign situation' in the murine
|
| virus from sexual transmission or
| |
| | antibody, it treats the whole molecule
|
| intravenous drug use, were offered a
| |
| | including the virus antigen as foreign.
|
| potentially life-saving therapy.
| |
| | LINK RECOGNITION MAY HOLD THE KEY
|
| Licensed in 1998, lamivudine is now used
| |
| | Dr. Rajan George, ViRexx Medical's vice
|
| in 120 countries as a standard therapy
| |
| | president of research and development,
|
| for chronic HBV carriers. The compound is
| |
| | told us, "The dendritic cells chop up
|
| also used in combination with other
| |
| | this protein into small pieces called
|
| drugs, such as protease inhibitors, for
| |
| | peptides, also known as epitopes. The
|
| HIV therapy. Development rights were
| |
| | dendritic cells have a system where they
|
| licensed to Glaxo Wellcome in 1990, which
| |
| | put the T-cell epitope on another
|
| is now sold under the brand name
| |
| | protein, MHC Class I, and bring it to the
|
| EpivirÂ(R). For his pioneering efforts
| |
| | surface of the dendritic cell. They are
|
| in developing the antiviral agent, Dr.
| |
| | presented as a complex on the surface of
|
| Tyrrell was awarded the gold medal by the
| |
| | the dendritic cell to attract the
|
| Canadian Liver Foundation and the
| |
| | T-cells." When the T-cells arrive to
|
| Canadian Association for the Study of
| |
| | inspect the foreign entity, the cytotoxic
|
| Liver in 2000. In 2005, he won the
| |
| | T-cells are activated. Then, they begin
|
| prestigious EnCana Principal Award for
| |
| | attacking and killing the virus-infected
|
| his development of the first effective
| |
| | cells.
|
| oral medication for Hepatitis B.
| |
| | Research at Tokyo's Cancer Institute
|
| HIS UNANSWERED QUESTIONS LAUNCHED A NEW
| |
| | Hospital, published in 1987 in Nippon
|
| HBV INVESTIGATION
| |
| | Sanka Fujinka Gakkai Zasshi, suggested a
|
| Despite the awards and recognition,
| |
| | feasibility of linked recognition of a
|
| questions remained for Dr. Tyrrell about
| |
| | virus antigen as a helper in tumor
|
| the shortcomings of lamivudine. He was
| |
| | immunity with a target antigen. In the
|
| troubled that some viruses would develop
| |
| | case of ViRexx Medical, Tyrrell's team
|
| resistance to the compound. "I was
| |
| | has created a new molecule, called
|
| disappointed the sustained viral response
| |
| | "chimigen." The term is shorthand for a
|
| was not complete," Tyrrell told us. In
| |
| | chimeric antigen, meaning it is an
|
| April 2003, the Journal of Antimicrobial
| |
| | antigen created from two different
|
| Chemotherapy published a study in Japan
| |
| | sources, part virus and part murine
|
| showing, "long-term (lamivudine) therapy
| |
| | monoclonal antibody.
|
| is associated with increased emergence of
| |
| | Dr. Tyrrell's work at ViRexx Medical with
|
| lamivudine-resistant strains of HBV."
| |
| | Dr. George suggested the
|
| Researchers concluded in this study, "The
| |
| | linked-recognition theory might be the
|
| therapeutic challenge to effectively
| |
| | key to breaking tolerance. Dr. George
|
| treat chronic HBV infection continues."
| |
| | emphasized, "The new 'chimigen'
|
| Having screened lamivudine for use in
| |
| | stimulates an immune response to the
|
| Hepatitis B at Glaxo's research lab at
| |
| | antigen as well as the viral antigen.
|
| the University of Alberta, Dr. Tyrrell
| |
| | This is very important because the virus
|
| was able to observe the immune response
| |
| | antigen was previously being ignored."
|
| of various HBV patients. "What really got
| |
| | That brings us back to why lamivudine had
|
| me interested in doing more work in this
| |
| | limited success. The immune systems of
|
| area was that we noticed patients, who
| |
| | some HBV carriers failed to recognize the
|
| have an immune response to the virus and
| |
| | viral infection as a threat to the body.
|
| take lamivudine, will have a better
| |
| | Tyrell's ViRexx Medical research team
|
| sustained response rate," Tyrrell
| |
| | hopes the body's immune system sees the
|
| explained. "A patient with elevated
| |
| | threat, thus stimulating the immune
|
| liver transaminases taking lamivudine had
| |
| | system, and breaking tolerance. It
|
| a higher probability of a sustained viral
| |
| | appears Dr. Tyrell may soon find out
|
| response," Tyrrell said with excitement
| |
| | whether or not the questions he asked
|
| in his voice. "In a patient with normal
| |
| | will bring the answers he hoped for.
|
