Cellular Immune Response
Mirror Effect® technology is designed to elicit a cellular immune response against tumors or pathogens, rather than an antibody response. A cellular immune response is the most effective way to eliminate pathogens or tumors that reside inside of cells. The most effective cells for eliminating diseased cells, which become diseased either due to internal genetic mutations and transformation into a tumor cell or due to an infection with a virus, is killer T-cells (“CTL”). CTL recognize antigens that exist inside, rather than outside, of a cell.
For T-cells to recognize internal antigens of a cell, they will surveille internal antigens that are displayed on surface on molecules called Major Histocompatibility Complex (MHC) class I. The MHC molecule displays small internally processed antigens within a groove. CTL surveille these MHC I molecules, which normally display normal self-antigens that do not trigger a kill response. However, when foreign or mutated antigens are detected by the CTL, along with a second “co-stimulatory” signal, the CTL kill response is executed.
Killer T-cells (CTL) recognize transformed tumor cells through interrogation of MHC I molecules through the T-cell receptor (TCR). The TCR scans peptide antigens displayed in the groove of major histocompatibility complex (MHC) class I receptors expressed on the surface of all nucleated cells. If the CTL encounters a MHC expressing a previously programmed tumor antigen, it will initiate a program to cause the disruption of the cell membrane to destroy the cells. This kill program requires both a positive signal through the TCR and a second “co-stimulatory” signal from a surface glycoprotein molecule on the tumor, such as CD80/CD86 interacting with the CD28 molecule on the CTL.
A major problem with design of therapeutic vaccines with a dominant cellular immune response is even if a neoantigen or viral antigen can be discovered that can program CTL to recognize tumors or viral infected cells, tumors and many viruses cause MHC I and co-stimulatory molecules to be down-regulated as a means to hide from the immune system. The Mirror Effect® solves this problem by use of ‘danger signals’