Computer Modeling Predicts Drug Target for Treatment of Epithelial Tumors

A computerized modeling system has been used to identify a potential target for chemotherapy that exists in a wide variety of epithelial tumors (carcinomas).

The target protein, CGEN-671, is a membrane splice variant of CD55, a known drug target for gastric cancer for which monoclonal antibody therapeutics are in clinical development. The existence of CGEN-671 was predicted by results obtained by Compugen Ltd. (Tel Aviv, Israel) using the proprietary Monoclonal Antibody Targets Discovery Platform. The existence of the predicted molecule was then validated experimentally in multiple epithelial tumors.

Initial experimental studies confirmed the existence of the predicted CGEN-671 transcript (mRNA) and demonstrated that it was highly expressed in colon carcinoma tissue as compared with normal colon tissue samples. CGEN-671's RNA 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 splice variant should be a superior drug target candidate for cancer treatment.

Immunohistochemical studies based on anti-CGEN-671 monoclonal antibodies showed that CGEN-671 was over expressed in more than 75% of tissue sections derived from colorectal cancer samples and had very low expression in most samples of normal colon tissue. In breast cancer, 75% of the tumor samples demonstrated significant over expression, while in lung cancer, 50% of the tumor samples had over expression compared with normal tissues.

These results from cancer and normal tissue sections strongly suggest significant potential for CGEN-671 as a drug target for clinical development of various types of monoclonal antibody drug therapy for colorectal, breast, and lung carcinomas, and possibly for additional epithelial derived tumors.

Dr. Anat Cohen-Dayag, president and co-CEO of Compugen said, "We are extremely pleased to see Compugen's continuing success in utilizing 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. The very exciting discovery and validation of CGEN-671 being announced today as well as the oncology target that is the subject of our recently announced collaboration with Bayer Schering Pharma (Leverkusen, Germany) are excellent examples of the unique capabilities obtained by combining synergistic predictive platforms, in these cases, alternative splicing and the identification of targets for monoclonal antibodies. After more than a decade building these capabilities, it is of course very gratifying to begin to see the results of these efforts."

Related Links:
Compugen Ltd.
Bayer Schering Pharma