Restoration of Immune Surveillance
The Pascal MHC-I Program consists of Intellectual Property and discoveries that target compounds that are active in the restoration of the immune system’s ability to recognize and destroy cancer cells.
MHC-I molecules (Major Histocompatibility Complex Class I) are found in varying numbers on the surface of most cells in the body. The function of MHC-I is to transport normal, abnormal and foreign protein fragments (peptides) to the surface of the cells where the fragments are then exposed to the immune system’s T cells. The MHC-I molecules are formed inside the cells (in the endoplasmic reticulum) and are then transported to the surface of the cells.
When presented on the surface of cells by MHC-I, the abnormal and foreign peptides, known as antigens, are recognized by antibody-like receptors on the T cells’ surfaces. The recognition of the antigens is a signal to the T cells that the cell is abnormal or has been invaded by a virus or other pathogen. As a result of these signals, the T cells trigger the invaded cell to destroy itself and its invaders.
Many cancer cells have the ability to interrupt or otherwise suppress the expression of antigens on their surfaces and in so doing, prevent the T cells from recognizing the cancer cells. One way in which cancer cells can interrupt this transport is through the suppression of the Transporter Associated with Antigen Processing (TAP), specifically, TAP-1, which transports antigens into the cell’s endoplasmic reticulum where the antigens can be inserted into MHC-I molecules for transport to the cell’s surface.
Cancer cells can also have the ability to suppress the production of MHC-I molecules in the endoplasmic reticulum. Whether either TAP-1 or MHC-I is suppressed, the effect is that the antigens are not made available for the T cells to recognize the cancerous cells, which are then free to replicate unhindered.
Pascal has acquired technologies that provide new methods for identification and development of drugs that can enhance and restore the production and action of both TAP-1 and MHC I.
On March 5, 2015, Pascal announced that it has demonstrated, in vivo, effective anti-cancer activity induced by new small-molecule drugs that make cancer cells more visible to the immune system. Pascal has identified several molecules for their ability to increase expression of proteins involved in the antigen processing pathway and in particular MHC-I molecules that display the tumour antigens on the surface of cancer cells.