CGEN-15001T is a membrane protein, which was predicted by Compugen to be a B7/CD28-like protein. The B7/CD28 protein family is known to be involved in regulation of the immune system in immune related disorders and in cancer. Protein expression studies indicate that CGEN-15001T is expressed on numerous types of cancer, such as carcinomas, sarcomas, melanoma and hematological cancers as well as on immune cells residing within the tumor. An antibody specifically recognizing CGEN-15001T demonstrated CGEN-15001T's expression in various solid cancers such as prostate cancer, melanoma, hepatocellular carcinomas, pancreatic islet cell carcinomas, and also in hematological malignancies such as Hodgkin's lymphoma, and T and B cell lymphomas. This expression on multiple cancer types is consistent with the expression of other known B7 proteins.
Furthermore, the expression of CGEN-15001T was observed in various subpopulations of immune cells, mainly macrophages and mast cells, in both tumor and normal tissue samples. This expression profile suggests a potential immunomodulatory role for CGEN-15001T in cancer therapy. This was further demonstrated by preclinical data obtained with CGEN-15001, which is the extracellular domain of CGEN-15001T fused to an Fc antibody fragment. In these studies CGEN-15001 was shown to inhibit activation of T cells, promote Th1/Th2 shift, and potentially induce immune tolerance, suggesting that this protein may help the cancer "silence" the immune responses towards the cancer cells. Blocking this function of CGEN-15001T through therapeutic antibodies would remove the suggested silencing effect of CGEN-15001T on the tumor, and would therefore enable the immune system to attack and destroy the tumor, thus serving as a very promising approach for cancer immunotherapy.
Taken together, the expression profile of CGEN-15001T and its proposed immunomodulatory profile suggest that a single therapeutic antibody against CGEN-15001T may attack cancer cells through three key mechanisms. One mechanism is by direct targeting and killing of the cancer cells expressing CGEN-15001T. Since CGEN-15001T is expressed on numerous cancers, an antibody against CGEN-15001T has therapeutic potential for various cancer indications. Another mechanism of the therapeutic antibody may be achieved by blocking the inhibition of the immune system induced by CGEN-15001T, whether expressed on the cancer cells and/or the immune cells within the tumor. And third, the same mAb for CGEN-15001T may promote the immune system component which acts against the tumor (Th1), while inhibiting the component which promotes the cancer (Th2). The significant potential of having all three mechanisms in a single therapeutic antibody to CGEN-15001T is being pursued actively by Compugen as part of its expanded mAb activities within its Pipeline Program.