| We interviewed Dr. Rajan George, Adjunct Faculty of | | | | antigen. It goes through the dendritic cell pathway |
| the University of Alberta's Pharmacy and | | | | and triggers the CTL response to clear the |
| Pharmaceutical Sciences Department. Dr. George is | | | | virus-infected cells. The system also produces |
| also Vice President of Research and Development for | | | | antibodies to viral antigens, which bind virus and viral |
| the Division of Infection Diseases of ViRexx Medical | | | | antigens and accelerate their removal. Because of the |
| Co. As part of the team of University of Alberta | | | | presence of the murine monoclonal antibody |
| scientists, a therapeutic vaccine is now being | | | | fragment, which is foreign to humans, along with the |
| developed which may inoculate against Hepatitis, | | | | antigen from the virus, the body's immune system |
| Anthrax and Avian Flu H5N1. The team of scientists | | | | treats this as a new threat and takes action. That is |
| includes internationally renowned Dr. Lorne Tyrrell, | | | | the immune response. |
| former Dean of Medicine at the University of Alberta, | | | | Interviewer: How would this work in treating Hepatitis |
| and Dr. Antoine Noujaim, Professor Emeritus of the | | | | B? |
| University of Alberta. | | | | Dr. Rajan George: Developing a treatment for |
| All three scientists are affiliated with ViRexx Medical | | | | Hepatitis B chronic infection, for someone who |
| Corp. On March 31st, the company announced it had | | | | already has the infection, would involve re-educating |
| entered into research collaboration with Defence | | | | the immune system to react differently than it |
| Research and Development Canada - Suffield (DRDC | | | | previously has. The infected person already has this |
| Suffield) to carry out research to evaluate ViRexx's | | | | virus and the derived antigens. If you put some more |
| proprietary Chimigen(TM) vaccine platform for | | | | of the same antigens into the person, the person's |
| biodefense applications. On April 6th, the company | | | | immune system is not going to know the difference |
| announced it had recruited procurement advocate | | | | His body is going to say, "Well, what's the |
| Frank Rapoport of McKenna Long & Aldridge to | | | | difference? I already have it. I am not going to do |
| pursue acquisitions of development contracts from | | | | anything with it." The body will ignore it. That's what |
| the U.S. Department of Defense and NIH with a | | | | is called tolerance. With the Chimigen(TM) therapeutic |
| particular focus on the potential of the Chimigen(TM) | | | | vaccine, we have changed the body's immune |
| technology in addressing biodefense and pandemic | | | | response to the virus. |
| threats. The company cited two of major targets | | | | Interviewer: How then have you changed the body's |
| would be, but not limited to, H5N1 avian flu and | | | | response to the infection? |
| anthrax. | | | | Dr. Rajan George: In a Hepatitis B chronic infection, |
| Interviewer: Can you describe ViRexx Medical's | | | | let's say I have the infection. My system is tolerating |
| Chimigen(TM) therapeutic vaccine? | | | | the virus. It's ignoring the presence of the virus. While |
| Dr. Rajan George: Chimigen therapeutic vaccine is | | | | that is happening, the virus may be causing disease in |
| used to produce immune responses in a host against | | | | with my liver. With time, it's going to get my liver into |
| infections which are difficult to produce immune | | | | trouble and my immune system has not responded |
| responses, by targeting the vaccine to dendritic cells. | | | | adequately to remove the threat. We inject the |
| The Chimigen platform can be extended to develop | | | | protein - the one we just produced, which we call |
| therapies for difficult-to-treat chronic infectious | | | | the Chimigen(TM) Therapeutic Vaccine - into the HBV |
| diseases. | | | | chronic carrier, a person who has a chronic hepatitis B |
| Interviewer: Does that mean the Chimigen platform | | | | virus infection. What happens is when our protein is |
| can be used to treat any infectious disease? | | | | administered, the dendritic cells are going to look for |
| Dr. Rajan George: Yes, except in cases where the | | | | anything new which enters the body. Those cells are |
| immune system is non-functional, as in the case of | | | | the immune system's first-line surveillance. The |
| HIV.The Chimigen platform can be used to produce | | | | dendritic cells are going to see this new foreign |
| either a therapeutic vaccine or a prophylactic vaccine. | | | | protein, and they are going to think that this is |
| This depends on the disease target and the antigen | | | | different from what was previously inside. Their |
| plugged into the platform. Some antigens have a use | | | | recognition of the molecule has changed from what it |
| in treating infection, while others have a use in | | | | was before. |
| preventing an infection. Either one would be targeted | | | | Before the virus protein was recognized as a "self" |
| to the dendritic cells. The therapeutic vaccine | | | | protein. Now it is being recognized as a "foreign" |
| generates a cytotoxic T cell response. A prophylactic | | | | protein. In chronic hepatitis B virus infection, the |
| vaccine would generate a B cell response and | | | | dendritic cells saw the virus as part of the "self" of |
| antibody production. | | | | the host, the vaccine changes the recognition of the |
| Interviewer: From the way you've described the | | | | virus protein as "foreign" to the host. |
| Chimigen(TM) vaccine, it appears potentially useful for | | | | Because the viral antigen is linked to the fragment of |
| many applications beyond Hepatitis B and C. How | | | | the mouse monoclonal antibody the direct the |
| broad are the applications? | | | | chimigen to dendritic cells it will enter the dendritic cell |
| Dr. Rajan George: We should be able to use this | | | | and be processed and stimulate an immune response. |
| platform for cancer therapy, depending upon the | | | | Interviewer: And after the vaccine injection, what |
| cancer antigen we use. We can plug in a specific | | | | does the body see? |
| cancer antigen into this platform, and the vaccine | | | | Dr. Rajan George: The body's immune system see a |
| targeted to dendritic cells. The dendritic cells would | | | | new foreign antigen composed of a portion of the |
| process and present the right antigen, then | | | | mouse monoclonal antibody linked to the viral antigen. |
| generating immune responses (T &B cell) against | | | | It's a foreign antigen." The new "chimigen" stimulates |
| the cancer. We are also evaluating some bioterrorist | | | | an immune response to the antigen as well as the |
| viruses, the biological weapons terrorists would use. | | | | viral antigen. This is very important because the virus |
| We just started a project to look at one of those | | | | antigen was previously being ignored. Now, it's being |
| viruses to see if we can come up with the | | | | recognized as foreign through linked recognition of |
| prophylactic vaccines to prevent diseases that would | | | | the mouse antigen as being foreign. |
| be caused by organism that could be used in | | | | Interviewer: How do the dendritic cells react after |
| bioterrorism | | | | they recognize this foreign threat? |
| Interviewer: Would the Chimigen(TM) vaccine be | | | | Dr. Rajan George: The dendritic cells are the sentries |
| effective as a prophylactic against avian flu, H5N1? | | | | of the immune system. They guard what comes in. |
| Dr. Rajan George: It could work for bird flu if we just | | | | When they recognize a "foreign situation," what does |
| plugged in the bird flu antigen into the platform. Then | | | | the immune system do? It treats the whole |
| we can use it as a prophylactic. It generates antibody | | | | molecule, the whole protein including the virus antigen, |
| to generate B-Cell response. You can produce a | | | | as foreign. The dendritic cells chop up this protein into |
| prophylactic vaccine using this platform. The | | | | small pieces called peptides. These peptides also are |
| Chimigen(TM) platform is quite adaptable. | | | | called "epitopes." There are T cell epitopes which are |
| Interviewer: How high is your confidence level in | | | | smaller, and B cell epitopes which are longer. These |
| producing a prophylactic vaccine for the avian flu | | | | small peptides bind to MHC I and activate Cytotoxic |
| virus? | | | | T lymphocytes (CTLs). The dendritic cells have a |
| Dr. Rajan George: My thinking is that it is quite high. I | | | | system where they put the T-cell epitope on another |
| think very highly of having a vaccine like that. But, | | | | protein, MHC Class I, and bring it to the surface of |
| the ultimate proof has to come from humans. Our | | | | the dendritic cell. They are presented as a complex |
| HepaVaxx B clinical trial will give us a lot of | | | | on the surface of the dendritic cell to attract the |
| information on how the technology really works. Until | | | | T-cells. The T-cells come and see this, then get |
| then, our optimism is based on laboratory results. | | | | activated. Now, the activation is also specific to the |
| Interviewer: Can you describe what comprises the | | | | virus protein. There are different varieties of T-cells, |
| Chimigen platform? | | | | but the cytotoxic T-Cells are the most important in |
| Dr. Rajan George: The platform has two components. | | | | eliminating infections that already exist. The activated |
| The first one is from the infectious agent. The | | | | cytotoxic T-cells are the ones who do the attacking. |
| second component is from a murine monoclonal | | | | They are the ones who start killing the virus infected |
| antibody. Part one is fused with a fragment of part | | | | cells. |
| two by recombinant technology to produce a new | | | | Interviewer: And what about the B Cells? |
| entity, the Chimigen(TM) vaccine. We are recombining | | | | Dr. Rajan George: That is the other side to this story. |
| one thing with another. We have a virus which has | | | | The dendritic cells can present another kind of |
| certain antigens. We take one of those, and we | | | | peptide epitope. There is a second class of peptides, |
| produce a recombinant molecule with the fragment | | | | which are also produced when the protein is chopped |
| we have taken from a murine monoclonal antibody. | | | | up. The dendritic cells stimulate the B-Cells, |
| Chimigen is the term we came up with to include the | | | | B-Lymphocytes. And B-lymphocytes produce |
| meaning of the full phrase, chimeric antigen. Chimeric | | | | antibodies. The longer peptides bind to MHC II and |
| means it comes from two different sources. We put | | | | activate B lymphocytes (B cells). B cells produce |
| them together and create a new molecule. One is | | | | antibodies against the peptides. The antibodies are |
| from the virus. The other one is from the mouse, | | | | specific to the antigens we put in the Chimigen(TM) |
| the monoclonal antibody. Now we have by | | | | Therapeutic Vaccine. Antibodies bind to viral proteins |
| recombinant methods produced a protein which is a | | | | that are on the surface of and block the ability of |
| chimeric protein. That's the Chimigen(TM) vaccine. | | | | the virus to bind to a target cell to cause an infection |
| Interviewer: How do you produce such a flexible | | | | and prevent the infection. This is the basis of a |
| vaccine, one that appears capable of treating nearly | | | | prophylactic vaccine. The antigen can bind to the |
| any infection? | | | | invading virus and form a complex that the body |
| Dr. Rajan George: To produce a Chimigen(TM) | | | | eliminates. The B-Cells produce antibodies against the |
| vaccine to treat nearly any infection, we start with | | | | virus antigen, which we have put in the Chimigen(TM) |
| an antigen (protein) from the infectious agent. We | | | | vaccine. |
| fuse it with a fragment called Fc of a mouse | | | | What do these antibodies do? The antibodies are |
| monoclonal antibody. This is done using recombinant | | | | specific to the antigen and bind to the viruses |
| methods. We end up with a new protein. This protein | | | | because they have the antigen. The system |
| is made in a cell culture of commercially available | | | | removes the virus by binding with the antibody. Also, |
| insect cells. The protein is produced by the insect | | | | the system removes infected cells using cytotoxic |
| cells. From the culture, we purify this particular protein | | | | T-lymphocytes. Both of these actions are achieved |
| that we made. The insect cell system is just a tool. | | | | by the Chimigen(TM) vaccine. |
| By virtue of its production in insect cells, the protein | | | | Interviewer: Aren't there a lot of antibodies being |
| attains special properties which are useful in | | | | investigated as therapeutics? |
| generating better immune responses. | | | | Dr. Rajan George: There are a lot of antibodies being |
| Producing this protein in insect cells gives it some | | | | investigated as therapeutics. OvaRex is the prime |
| very peculiar properties, which are different from our | | | | example. Avastin and Herceptin are two others, both |
| own mammalian proteins. Once we have it coming | | | | of which are doing very well in the market. Another |
| out of the cell, we purify it and make it really pure. | | | | is Remicade, which is used to treat diseases such as |
| Now we have a protein with the virus antigen murine | | | | rheumatoid arthritis. There are antibodies that are in |
| monoclonal antibody with modified properties. This is | | | | various stages of clinical development, many are |
| a totally new entity. | | | | humanized antibodies where you want to avoid an |
| Interviewer: What do you mean when you say, | | | | immune response to the antibody. Our chimigen |
| "useful in generating better immune responses"? | | | | technology is new as we are trying to increase the |
| Dr. Rajan George: When a person has a chronic virus | | | | immune response on a virus or a cancer through |
| infection, his or her body ignores the virus and | | | | linked recognition. It is not found anywhere outside |
| associated proteins. The body treats the virus as | | | | of our laboratories. This approach has not been tried |
| part of itself. The body does not recognize this virus | | | | before for chronic HBV or HCV infections. |
| as something foreign to it. Therefore the immune | | | | Interviewer: Why would your vaccine work where |
| system does not attack the virus. But, by combining | | | | others have tried and failed? |
| the virus antigen with a foreign protein such as the | | | | Dr. Rajan George: The reason is because of the |
| murine antibody fragment, the whole chimeric protein | | | | novelty of the technology. We are re-educating the |
| now is recognized by the body's immune system as | | | | body's own immune system to do the work by using |
| "foreign," different from something of its own. In | | | | the Chimigen(TM) technology. When you inject a |
| essence, this is a re-education of the immune system | | | | xenotypic antibody , that is a non-human antibody |
| to switch its recognition of the virus from "self" to | | | | that is linked to a specific antigen. The body |
| "foreign". | | | | recognizes the whole molecule as foreign and |
| Interviewer: From where did the scientific model | | | | produces immune responses with both T- and B-Cell |
| come, and does it have similarities to another ViRexx | | | | immunity. We believe that this enhanced immune |
| Medical product, OvaRex MAb®? | | | | response will be helpful in controlling the viral infection |
| Dr. Rajan George: This scientific model arose from | | | | in the case of viral chimigens. |
| discussions among the three lead scientists of the | | | | Interviewer: Much of the research has been within |
| company, Dr. Tony Noujaim, Dr. Lorne Tyrrell, both | | | | the laboratory. How much of this is hypothetical? |
| founders of the company and myself. I am a | | | | Dr. Rajan George: Our experiences so far have been |
| biochemist by training and the collective thoughts of | | | | mostly with isolated systems, meaning experimental |
| all of us went into the design of the Chimigen(TM) | | | | systems outside of the body. For example, ViRexx's |
| platform. One major similarity between Chimigen and | | | | Chimigen(TM) vaccine for treating chronic hepatitis B |
| OvaRex is that both involve a murine monoclonal | | | | infection is what we call HepaVaxx B. This is waiting |
| antibody. Another similarity is that both target | | | | to go into Phase I clinical trials. We have done a lot |
| dendritic cells. The Chimigen model came from | | | | of ex vivo experiments in the lab to evaluate the |
| thoughts about targeting dendritic cells, but without | | | | immune responses it can produce. We showed what |
| the use of antibodies. OvaRex is a murine monoclonal | | | | we had predicted in theory has been true. We have |
| antibody against the cancer antigen CA-125. The | | | | also done some animal experiments, where the |
| Chimigen(TM) vaccine has a fragment of a murine | | | | vaccine showed similar effects, again, as predicted. |
| monoclonal antibody. OvaRex needs the CA-125 | | | | For HepaVaxx B, the animal results are also showing |
| antigen in a cancer patient to bind to. The bound | | | | great progress and promise. We believe the Phase I |
| complex goes to the dendritic cells. The | | | | studies will show safety and maybe some |
| Chimigen(TM) vaccine does not need to look for the | | | | immunological data. The advanced clinical trials, Phase |
| antigen in a patient because it already has the | | | | II and III, will tell us exactly what happens in humans |
| relevant antigen built in it. | | | | (efficacy) with a chronic infection of Hepatitis B. I |
| Interviewer: It sounds as though the Chimigen(TM) | | | | believe the Chimigen(TM) vaccine platform can make |
| vaccine acts in a similar way to OvaRex® in | | | | a difference in the area of immunotherapy of |
| dealing with a hostile threat to the body's health. How | | | | infectious diseases and cancer. |
| do they differ? | | | | For HCV, there is neither a therapeutic vaccine nor a |
| Dr. Rajan George: There are similarities and there are | | | | prophylactic vaccine available in the market right now. |
| differences. OvaRex binds to the antigen CA-125. | | | | Current available therapies are not very efficient, are |
| Then, the CA-125/Ovarex complex binds to the | | | | expensive and have severe side effects. We do |
| dendritic cells. The complex is internalized and | | | | need more effective vaccines, both prophylactic and |
| processed. The peptides generated from the antigen | | | | therapeutic, to prevent new hepatitis C virus |
| are presented to the T cells, and the chain of events | | | | infections and to eliminate existing infections. It is not |
| in the immune system gets stimulated. The activated | | | | an easy challenge but hepatitis C is an important |
| cytotoxic T cells eliminate the cancer cells which | | | | target. |
| contain the CA125 antigen. In the case of the | | | | COPYRIGHT © 2007 by StockInterview, Inc. |
| Chimigen(TM) vaccine, the vaccine itself contains the | | | | ALL RIGHTS RESERVED. |