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