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Immunotherapy innovation spurs 'remarkably aggressive immune response'

1st April 2013


Biotechnology innovator TapImmune Inc has engineered a remarkable, yet elegantly simple, way for the body to recognise tumour and infectious disease cells and provoke an aggressive immune response whereby the body’s own killer T-Cells attack and eradicate harmful foreign bodies.  This with respect to any form of cancer or disease via a technology that’s entirely non-discriminate in helping the body eradicate dangerous cells of many kinds.
 
Underscoring the vast potential of TapImmune’s approach is its exclusive licensing option agreement with the Mayo Clinic for a breast cancer antigen technology complementary to the company’s TAP (AdhTAP) protocol. In a novel approach, TapImmune and the Mayo Clinic will co-develop a specialized vaccine for patients with very aggressive HER2/neu breast cancer. What’s unique is that TapImmune’s technology actually re-activates the body’s own immune system, triggering mission-critical self-curative mechanisms that would otherwise not function properly.
 
“We chose to work with the Mayo Clinic because they have great clinical expertise in breast cancer, and we’re focusing specifically on HER2/neu breast cancer because we found complementary technology with Mayo that will work with TAP and address the problems found with earlier approaches,” explains Dr. Glynn Wilson, chairman and CEO of TapImmune. “Importantly, we’re able to work with a leading expert on breast cancer vaccines, Dr. Keith Knutson of the Mayo Clinic, who will conduct the trials. Through these trials, we’ll also address a huge clinical need for patients who express low to moderate levels of HER2/neu and are not candidates for treatment with Herceptin(R) (trastuzumab), an intravenously delivered monoclonal antibody.”
 
Simply put, TAP (transporters associated with antigen processing) plays a major role in the complex human immune system. When foreign bodies (viruses and disease) attack cells in the body, the normal response is for killer T-cells to find those invaders and destroy them. TAP is a transporter that helps trigger an immune response by providing a pathway for tumour antigens to be expressed on the surface of the cell.  In most solid cancers TAP levels are greatly reduced, which prevents the antigen presentation required to stimulate T-cells into action.
 
In the treatment of cancer, TAP is analogous to turning on the light bulb on the surface of tumor cells, allowing immune cells to “see” them and inspire action accordingly.  For infectious disease treatment, TAP turns the light bulb to a higher intensity to prompt more immune cells to act. TAP potentially allows the immune system to see everything that’s foreign on the surface, in contrast to other approaches that simply focus on a single tumor antigen to try and raise an immune response.  Indeed, TapImmune’s technology is entirely unique in that it isn’t dependent on genetics like other immunotherapies and doesn’t directly target the tumor cells, but instead assists the body’s own immune system to do what it was designed to do by turning the TAP back on and activating destroyer T-Cells into “kill” mode.  See a more detailed explanation of the science of TAP below.
 
Wilson says with any vaccine, there are two requirements needed to create a good immune response: 1) stimulate the cytotoxic lymphocyte (Class 1 pathway) and 2) stimulate the pathway that stimulates the T helper cells (Class 2 pathway), which gives a long-lasting immune response.  The failure to satisfy both of these requirements is one of the reasons other breast cancer vaccines have not progressed.
 
“For breast cancer, we are developing a unique multi-component vaccine that stimulates the Class 2 pathway (CD4 – helper cells) for a prolonged immune response and the Class 1 pathway (CD8 – cytotoxic T cells) to activate killer T-cells that will infiltrate and destroy tumor cells. The HER2/neu vaccines that had been tested in the past either do not stimulate sufficient cytotoxic T-cell response on the Class I pathway or they do not give a long-lasting effect. I realized that we have the capability here with the Mayo technology plus TAP of creating good responses on both sides of the immune system required for a good vaccine. It is a very innovative, creative and exciting approach.”
 
TapImmune President and CFO Denis Corin agrees. “I think there are a lot of vaccine candidates that have gone through the mill and probably failed at Phase 2 or Phase 3 predominantly because the immune recognition and immune stimulation hasn’t been as effective as they needed it to be to come up with an end-level product. TAP is elegantly simple and we believe applicable across multiple types of cancers.”

“In the overall vision of the use of cancer vaccines, the ultimate goal is to have vaccines that can be used prophylactically at the earliest detection of pre-cancerous conditions like DCIS,” Corin continues.  “It is thought that the more advanced the cancer, the lower the TAP levels will be. TAP may be applicable to all stages of cancer if we consider experiments that treated smallpox, augmenting the normal levels of TAP and making a smallpox vaccine fully 100 to 1,000-fold more potent.”

The immune system distinguishes normal and cancerous (or virus-infected) cells by monitoring major histocompatibility complex (MHC) class I, a molecule on the cell’s surface. Nearly all cell types display MHC class I antigen on their surface, continually providing information to the immune system. The MHC molecule, which contains small protein fragments (peptides), cycles to the surface of the cell to present foreign antigens to the cellular immune system, thereby activating the cytotoxic T-cells to  kill virus-infected or cancerous cells.
 
In many cancers, there is a disruption in the process and the MHC on the cell surface is missing the tumor antigen peptides that identify the cell as being cancerous. They are basically hidden from the immune system and grow into tumors that eventually kill the person. Because TAP is affected negatively in the disease process, TapImmune’s vaccine technology turns TAP back on, supplying peptides to the MHC class I molecule. TAP facilitates the binding of foreign peptides to the MHC class I molecule. TAP facilitates the binding of foreign peptides to the MHC class I complex, displaying them on the cell’s surface. Cytotoxic T-cells recognize them as foreign and ultimately neutralize and destroy abnormal cells.
 
Clinical studies on melanoma when examining primary and metastatic (spreading) tumors show a clear and significant correlation between TAP expression and survival. 
 
TapImmune (formerly GeneMax) was formed in Vancouver, British Columbia, in the laboratories of immunologist Wilfred Jeffries.who with his colleagues produced exciting data showing that administration of TAP to replace deficient levels in tumours or augment natural levels in viral disease had significant therapeutic effects in animal models.  Four years ago, TapImmune principals acquired the technology and intellectual property outright from the university and set out to put together a board of directors and advisory board that understands the technology and its potential and to partner with credible collaborators like the Mayo Clinic and Aeras Global TB Vaccine Foundation, an organization largely funded by the Gates Foundation.
 
“In discussions with Aeras Global TB Vaccine Foundation, we identified the potential of TAP for use in the joint development of their next-generation TB vaccine,” said Denis Corin, TapImmune’s president and CFO. “But you could also look at influenza, SARS, HIV H1N1 and many other societal pathogens.  We’re also working with Dr. Poland and the Mayo Clinic on a new small pox vaccine. But, small pox is the tip of the iceberg. There are a number of nasty viruses that are potential bioterrorism threats and governments around the world could stockpile our TAP vaccine and call on it in the event of a bioterrorist threat.”

For more information, visit www.tapimmune.com





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