Compugen has reported 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. Compugen has filed patent applications covering 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 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 sequence present in CGEN-671’s extracellular domain that is not present in CD55. The 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.
Reportedly, 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 over expression. In lung cancer, 50% of the tumor samples had over expression compared with normal tissues.
IHC results from diseased and healthy tissue sections strongly suggest 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.
Anat Cohen-Dayag, president and co-CEO of Compugen, said: “We are extremely pleased to see Compugen’s continuing success in utilising its predictive platforms to discover previously unknown candidate molecules in key areas of unmet medical need. Also, of major significance for us is the fact that we have reached the point where we are now using multiple predictive capabilities in combination to accomplish this.”