Compugen Ltd. has announced results demonstrating the therapeutic potential of CGEN-15001T as a drug target for treatment of multiple cancers by means of monoclonal antibody ("mAb") therapy.
These results 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.
These findings, together with previous results supporting its active immunomodulatory effect, strongly support CGEN-15001T's potential as a powerful drug target for treatment of various solid and hematological cancers, an area of great interest to the pharmaceutical industry.
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.
Initial validation results previously demonstrated that CGEN-15001T is expressed in both prostate cancer cells as well as in immune cells residing within the tumor.
The results being reported are based on recently completed studies using an antibody specifically recognizing CGEN-15001T. These studies were designed to analyze in greater detail the protein expression levels of CGEN-15001T in multiple cancers of interest.
In these studies CGEN-15001T's expression was demonstrated in various solid cancers in addition to prostate cancer, including 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 performed by Compugen, 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.
Dr. Anat Cohen-Dayag, CEO of Compugen, remarked, "Immunotherapy is one of the most promising new approaches for the treatment of various cancers, and within this field, mAb immunotherapy appears to be the most rapidly growing segment. The mechanisms by which mAbs fight cancer are very versatile, including "tagging" the malignant cell so that it is better recognized by the immune system, and blocking signals that promote growth and survival of cancer cells.
Dr. Cohen-Dayag concluded, "We are extremely pleased to report that our studies to date with CGEN-15001T, the first of our nine novel B7/CD28-like proteins to undergo these studies, indicate that a mAb against this novel target provides the opportunity for treating multiple cancer indications of various origins through several mechanisms of action, in order to promote an immune attack on cancer cells."