New Study Explores Immune System Stimulation In Battle Against HER-2/neu Positive Breast Cancer

The Mayo Clinic is excited to announce a Phase I study of a new therapeutic vaccine in HER-2/neu positive breast cancer patients in the fourth quarter of 2011. To understand the importance of this development, the HER-2/neu and the significance of HER-2/neu positive breast cancer must be examined.

Due to a genetic change, cancerous cells produce an excess of HER2 in approximately 1 in 5 breast cancer cases as well as in other forms of cancer. For unknown reasons, HER2-positive breast cancers are less responsive to hormone treatment and tend to be more aggressive than other types of breast cancer.

HER-2/neu is a protein homologous to epidermal growth factor receptor providing growing, dividing and repair signals to cells. Whilst healthy breast cells contain 2 copies of the HER2 gene, some forms of breast cancer develop when a breast cell contains 2 or more copies of the gene which results in over-production of HER2 protein (over-expression) leading to increased growth and division of the affected cells.

HER-2/neu is over-expressed on the cell surface of several cancers, including breast, colorectal, ovarian, and pancreatic carcinomas, supporting the malignancy of several tumors with poor prognosis in cancer patients. With HER-2/neu expressing ~20% to 30% of breast and ovarian cancers it has been identified by the National Cancer Institute as one of the top priorities for the development of cancer drugs.

The common treatment for HER-2/neu positive patients is Herceptin (trastuzumab), a monoclonal antibody that targets HER-2/neu receptors on cells, however, the treatment results in a significant amount of patients (estimated to be ~70%) failing to respond or losing their responsiveness. The authors recommend more widely applicable therapies for this patient population.

So far, previous attempts to develop a vaccine against the Her-2/neu protein proved unsuccessful in overcoming the difficulty of developing a robust and a long-acting immune response by positively stimulating cytotoxic T-cells and T-helper cells in the immune system, which is necessary for a successful vaccine, however, some previous trials managed to progress to clinical trials.

Once stimulated, cytotoxic T-cells identify cancer cells, infiltrate tumors and kill abnormal cells, with T-helper or T-memory cells being responsible for long-term memory, enabling the immune system to continuously recognize abnormal cells.

It has been determined that the function of TAP (Transporters Associated with Antigen Processing – reference 1 provides further background) is significantly reduced in many cancers due to inadequate stimulation of cytotoxic T-cells, resulting in poor recognition of cancer cells. The process can be re-instated by replacing TAP through TapImmune’s AdhTAP1 technology, which is similar to turning on a light bulb allowing these cells to ‘see’ tumor cells.

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

In their clinical evaluation, The Mayo Clinic will be assessing the proficiency of two technologies, the unique peptide antigen and the combination of TapImmune’s, TAP vector technology, to stimulate an immune response in HER-2/neu breast cancer patients and to improve patient prognosis and survival rates.

In a concluding statement the authors said,

“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,”

..continuing that,

“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.”

Written by Petra Rattue
Copyright: Medical News Today

Not to be reproduced without permission of Medical News Today

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

2. Pharma (2011), March/April, 32-34

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