Joint Project Underway to Develop Therapeutic Vaccine for Treatment of Breast Cancer

A collaborative project is underway to develop a therapeutic vaccine for the treatment of breast cancer.

The immune system is able to distinguish between normal cells and cancerous or virus infected cells by monitoring the major histocompatibilty complex (MHC) class I on the surface of cells. The MHC molecule contains a peptide, which in combination with the MHC molecule, is able to stimulate the killer T-cells of the immune system. This peptide fragment is derived from the degradation of cellular proteins within the cytoplasm of the cell by the proteasome enzyme complex. These peptides are transported into the subcellular endoplasmic reticulum (ER) by transporters associated with antigen processing (TAP). Inside the ER peptides combine with other proteins to form functional MHC class I (MHC plus peptide). The functional MHC is transported to the surface of the cell where the functional MHC complex is presented to the immune system.

Functional MHC molecules generated from normal peptides within normal cells do not stimulate the killer T-cells of the immune system. However, if the peptide fragments are not normal because they were generated from viral proteins inside an infected cell (viral antigens) or from proteins made exclusively by cancerous cells (tumor antigens) then stimulation of killer T-cells occurs. The killer cells then multiply and kill the abnormal virus infected cell or cancerous cells.

In most solid cancers TAP levels are greatly reduced, which prevents the antigen presentation required to activate killer T-cells. To overcome this problem TapImmune Inc. (Seattle, WA, USA) developed the AdhTAP method for restoring TAP expression in solid tumors. The method depends on a delivery of the TAP gene by a vector, which results in expression of significant MHC, activation of killer T-cells, and destruction of the tumor.

This technology is now being refined for treatment of breast cancer in a joint project conducted at the Mayo Clinic (Rochester, MN, USA).

"We chose to work with the Mayo Clinic because they have great clinical expertise in breast cancer, and we are 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,” said Dr. Glynn Wilson, chairman and CEO of TapImmune. "Importantly, we are 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 trastuzumab, an intravenously delivered monoclonal antibody.”

Related Links:
TapImmune Inc.
Mayo Clinic