Therapeutic Target RENCAREX®
CA IX Antigen – A Highly Specific Tumour Target
RENCAREX® (INN: Girentuximab) binds specifically to the protein carbonic anhydrase IX (CA IX, MN, or G250 antigen). CA IX is expressed on the cell surface in over 90% of all clear cell RCC, but not expressed in normal kidney tissue. The antigen is also present in a variety of other solid tumours, including head&neck, cervical, colon, breast, and non-small cell lung cancer. The antigen is expressed at low levels in the gastric epithelium, upper intestinal tract epithelium, and the bile ducts, but is undetected in normal kidney and other tissues.
Fig.: IHC Staining Illustration of RCC and healthy kidney tissue shows the high specifity of the antibody. The antibody does not bind to normal kidney tissue (greyish area, lower right) but stains specifically only renal cell cancer (brownish area, upper left).
Mode of Action of RENCAREX®– ADCC
The antibody Girentuximab binds to the CA IX antigen expressed on the tumour cells, thereby triggering an immune reaction called Antibody-Dependent Cellular Cytotoxicity (ADCC). Through this mechanism, effector cells, e.g. NK (natural killer) cells, of the immune system are activated to kill the tumour cells.
Fig.: ADCC mechanism of action. The variable region of the antibody Girentuximab binds to CA IX expressed on the tumour cells. The constant region of Girentuximab binds to the Fc receptor of natural killer cells (NK cells). NK cells act as effector cells, which destroy the tumour cells.