TapImmune Inc. Release: Killers and Helpers-Stimulating the Immune System to Fight Her-2/neu Positive Breast Cancer

August 16, 2011 -- The start of a new clinical program is a key milestone for those of us that have been fortunate to be involved in taking promising research into product development. Therefore, we are excited by the Phase I studies that will start in the fourth quarter of 2011, at the Mayo Clinic, on trials of a new therapeutic vaccine in HER-2/neu positive breast cancer patients.

In order to understand the importance of this development, we must first look at HER-2/neu and the significance of HER-2/neu positive breast cancer.

In about 1 of every 5 breast cancer cases, the cancerous cells produce an excess of HER2 due to a genetic change. This genetic change and the elevated levels of HER2 that it causes can occur in many types of cancer.

These HER2-positive breast cancers tend to be more aggressive than other types of breast cancer and they are also less responsive to hormone treatment.

Why this happens is no mystery. HER-2/neu is a protein homologous to epidermal growth factor receptor .which provides signals to your cells, telling them to grow, divide, and make repairs. A healthy breast cell has 2 copies of the HER2 gene. Some kinds of breast cancer get started when a breast cell has more than 2 copies of that gene, and those copies start over-producing the HER2 protein. As a result, the affected cells grow and divide much too quickly.

In other words, HER-2/neu is over-expressed on the cell surface of several cancers, including breast, colorectal, ovarian, and pancreatic carcinomas.

Over-expression of this protein results in the maintenance of the malignancy of several tumors and is associated with poor prognosis in cancer patients. Accordingly, the National Cancer Institute has identified HER-2/neu as one of the top targets for cancer drug development.

As HER-2/neu is expressed in ~20% to 30% of breast and ovarian cancers it has become a key target in the fight against this type of breast cancer. The standard of care for patients who present as HER-2/neu positive is Herceptin (trastuzumab), which is a monoclonal antibody that targets the HER-2/neu receptor on cells, however, a large percentage (estimated to be ~70%) of HER-2/neu positive patients will either not respond or loose responsiveness to this drug. Thus, there is a pressing need for more widely applicable therapies for this patient population.

There have been a number of efforts to develop vaccines against the Her-2/neu protein, and several have progressed to clinical trials, however, progress with this approach has generally been hampered by the difficulty of developing a robust and a long-acting immune response required for a successful vaccine. To achieve this requires good stimulation of two types of cells in the immune system, namely cytotoxic T-cells and T-helper cells.

Cytotoxic T-cells lead the immune fight as once stimulated they recognize cancer cells, can infiltrate tumors and kill abnormal cells. In contrast, T-helper or T-memory cells provide the long-term memory that allows the immune system to continuously recognize abnormal cells.

It has been well established that in many cancers, the function of TAP (Transporters Associated with Antigen Processing – reference 1 provides further background) is greatly diminished. Under these circumstances stimulation of cytotoxic T-cells to recognize cancer cells is poor. Replacement of TAP through TapImmune’s AdhTAP1 technology can re-instate this process and stimulate cytotoxic T-cells, analogous to turning the light-bulb back on to allow these cells to “see” tumor cells.

In addressing the stimulation of T-helper cells, Dr Keith Knutson and colleagues at the Mayo Clinic, together with collaborators, discovered a novel set of peptides (HER-2/neu antigens – reference 2 provides further background) that stimulated these cells in ~ 80% of HER-2/neu positive patients.

In our clinical programs we will be examining the ability of both technologies to stimulate an immune response in HER-2/neu breast cancer patients and to improve their prognosis and survival. Clinical evaluation of the novel peptide antigens from the Mayo Clinic will be followed by the combination with TapImmune’s, TAP vector technology. We believe that this approach which stimulates two key components of the cellular immune system in HER-2/neu breast cancer patients could have a significant advantage with respect to strength and duration of the immune response. We envisage that the approach will result in an injectable product that will be simple to manufacture.

The initial clinical pathway of cancer vaccines is generally to seek approval for products that can be used as therapeutic vaccines to improve patient survival. However, our ultimate vision on the future use of such vaccines, for the treatment of breast cancer, is to have prophylactic vaccines that can be used at the earliest stage of disease diagnosis, e.g. in situ ductal carcinoma.

For those of us who have lost loved ones to breast cancer, who initially presented with this indication, the importance of this goal cannot be overstated.


1. L. Karyampudi et al (2010), Clin.Cancer Res.16, 825-833

2. www.pharmamag.com(2011), March/April, 32-34


Jim Morham

Market Media Connect LLC



Dr Glynn Wilson

Chairman & CEO

TapImmune Inc.

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