Compugen Discovers Drug Target for Treatment of Epithelial Tumors
News Dec 29, 2009
Compugen Ltd. has announced the discovery and experimental validation of CGEN-671, a new drug target for multiple epithelial tumors. CGEN-671 is a membrane splice variant of CD55, a known drug target for gastric cancer for which monoclonal antibody (mAb) therapeutics are in clinical development by others.
The potential application of CGEN-671 as a drug target was initially predicted in silico by Compugen through the use of its Monoclonal Antibody Targets Discovery Platform; the predicted molecule was then validated experimentally in multiple epithelial tumors.
Epithelial tumors, also referred to as carcinomas, account for approximately 85% of all cancers, including the ten most prevalent cancers in the western world, such as breast, colorectal, lung, ovary, prostate and skin. Compugen has filed patent applications covering this novel splice variant and its various therapeutic and diagnostic utilities.
Initial experimental studies confirmed the existence of the predicted CGEN-671 transcript (mRNA) and demonstrated that, compared with normal tissue samples, it is highly expressed in colon carcinoma tissue. Furthermore, in these mRNA experiments, CGEN-671’s expression level in various healthy tissues was up to 200 times lower than the expression level of the previously known cancer target CD55, suggesting that the Compugen discovered splice variant should be a superior drug target candidate for cancer treatment.
In addition, the in silico prediction of CGEN-671 identified a unique sequence present in CGEN-671’s extracellular domain that is not present in CD55. This sequence allows for the development of antibodies that specifically bind to CGEN-671 and do not recognize CD55.
Recently concluded immunohistochemistry (IHC) studies, by independent pathologists using CGEN-671 specific antibodies, further confirmed the predicted potential for CGEN-671 to serve as a therapeutic mAb target for colorectal, breast and lung cancer.
In these studies, it was shown that CGEN-671 was over expressed in more than 75% of the tissue sections derived from the colorectal cancer samples and had a very low expression in most samples of normal colon tissue. Similar results were seen in breast cancer, where 75% of the tumor samples demonstrated significant over expression. In lung cancer, 50% of the tumor samples had over expression compared with normal tissues. These IHC results from diseased and healthy tissue sections strongly suggest significant potential for CGEN-671 as a drug target for clinical development of various types of mAb drug therapy for colorectal, breast and lung carcinomas, and possibly for additional epithelial derived tumors.