Are CD46, CD55 and CD59 good targets for the treatment of malignant disease?

Authors Avatar
BM301 Fundamental Immunology | Essay

Fundamental Immunology: Are CD46 - CD55 - CD59 good targets for the treatment of malignant disease?

Are CD46 - CD55 - CD59 good targets for the treatment of malignant disease?

Clusters of differentiation which is often abbreviated to CDxx (xx representing a number specific to each CD molecule), is a naming system developed in 1982 to recognise surface molecules present on white blood cells that were recognised by monoclonal antibodies (Fiebig et al., 1984). They can perform a number of functions such as acting as receptors or ligands and are usually involved in cell signalling, causing a cascade in certain immune responses. There are now over 250 proteins that are classified as CD molecules (Zola et al., 2005). This essay will look at three clusters of differentiation - CD46, CD55 and CD59 - known membrane proteins that protect against native complement damage (Xu et al, 2008) and conclude whether or not they are good targets in the treatment of malignant disease.

CD46 (Membrane Cofactor Protein) is a type I membrane protein which acts as a complement receptor. It is a cofactor for the proteolysis of C3, so cells displaying CD46 will be protected from attack by the native complement system (Assem et al., 2005). CD55, which is also known as Decay Accelerating Factor is also a membrane protein with a similar function to CD46. CD55 causes a reversible reaction whereby it stops C3 convertases forming or accelerates the decay of convertase that has already formed. This prevents the formation of the membrane attack complex which is a group of four complement proteins (C5b, C6, C7 and C8) and many C9 molecules which form an open ended barrel like structure in the membrane of the target cell (this is essentially what destroys the cell) (Tschopp et al., 1986). The third membrane CD protein is CD59 (also called protectin) interacts with the end molecules of the complement cascade - C8 and C9 - binding to C5b678 and preventing the binding and replication of C9. Thus, the membrane attack complex (MAC) cannot form. These three proteins are thought to act together as an effective barrier to autologous complement damage (Simpson et al, 1997).
Join now!

As well as being a receptor for a particular strain of the measles virus and human herpes virus-6, CD46 has also shown to be present on malignant cells in higher concentrations than in normal cells. This goes some way to explaining why cancer cells can protect themselves from the complement system (Assem et al., 2005). Further studies on tumours have suggested that the expression of these three proteins may be different in tumours than to normal cells, and that they may play a role in tumour survival (Simpson et al, 1997).

One study in particular, carried ...

This is a preview of the whole essay