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Compugen validates cancer immunotherapy prospect
TEL AVIV, Israel—In its sixth major announcement in recent months, Compugen has unveiled CGEN-15027, a novel immune checkpoint candidate with promising validation data for involvement in tumor immunology. The experimental results include its expression in the cancer microenvironment, both on cancer cells derived from lung, breast and liver cancer patients and on tumor-infiltrating immune cells. In addition, the disclosed data demonstrate CGEN-15027’s inhibitory effect on cancer-specific immune cells. These results suggest that CGEN-15027 has strong potential to serve as a target for monoclonal antibody cancer therapy with a mechanism of action that is potentially distinct from previously disclosed Compugen checkpoint target candidates.
CGEN-15027 is one of 11 novel B7/CD28-like immune checkpoints candidates discovered to date through the use of Compugen’s proprietary predictive discovery infrastructure, and is the sixth of these 11 for which experimental data have been disclosed demonstrating their potential to serve as targets for cancer immunotherapy. The different characteristics of each of Compugen’s immune checkpoint candidates suggest that these drug target candidates may give rise to different first-in-class cancer therapeutics.
In July the company announced that it had achieved the first milestone in its cancer immunotherapy collaboration with Bayer HealthCare and would receive a $1.2 million payment for one of two checkpoint protein candidates. Overall, a total of $30 million potential milestone payments are associated with the program.
Dr. Anat Cohen-Dayag, Compugen’s president and CEO, stated, “Six of our 11 computer-predicted novel immune checkpoint candidates have demonstrated initial successful biological validation supporting their involvement in tumor immunology. To our knowledge, this hit rate is unprecedented. Furthermore, the remaining five are undergoing further validation studies. These results not only support the strength and breadth of our Pipeline Program, but also attest to the impressive power and accuracy of our unique predictive discovery infrastructure.”
Cohen-Dayag tells DDNews that “Compugen invested over a decade in building a unique predictive discovery infrastructure designed to create biological knowledge from the integration of different types of data, such as genome, molecular and disease data. We have an optimized process to model biological phenomena and have applied it to create a vast repertoire of robust predictive algorithms. We leverage this infrastructure to continuously extract novel discoveries from our platform.”
“Each of our disclosed immune checkpoint candidates is distinct, as these are distinct genes,” Cohen-Dayag adds. “They also differ in their pattern of expression and/or mode of action. With respect to CGEN-15027, we are very pleased with the experimental data now being disclosed, based on which we have initiated a therapeutic antibody discovery program against this promising immune checkpoint candidate.”
Initial experiments with CGEN-15027 have demonstrated inhibitory activity in melanoma-specific human CD8 cytotoxic T cells, which are immune cells that recognize and destroy cancer cells. Overexpression of CGEN-15027 on these cells dampened their cancer specific reactivity consistent with a role of an immune checkpoint. These findings, indicating that CGEN-15027 exerts its inhibitory effect upon its expression on T cells, support a mechanism of action that is potentially different from previously disclosed Compugen checkpoint target candidates. CGEN-15027 was found to be expressed on effector immune cells within the tumor microenvironment. Expression of CGEN-15027 was also detected on human effector immune cells, such as natural killer and T cells, which play important roles in antitumor immunity, further substantiating a role for CGEN- 15027 in tumor immunology. In addition, CGEN-15027 was shown to be expressed on cancer cells derived from patients with lung, breast and liver cancer.
Immune checkpoint inhibitory receptors and their ligands are crucial for the maintenance of self-tolerance (that is, the prevention of autoimmunity) and for the protection of tissues from damage when the immune system is responding to pathogenic infection or other injuries. These immune checkpoints, which are “hijacked” by tumors to block the ability of the immune system to destroy the tumor (immune resistance), have lately emerged as potential game-changers and promising targets for cancer immunotherapy. Therapeutic blockade of immune checkpoints can boost antitumor immunity, enabling the patient’s immune system to recognize and attack the tumor cells and mount durable antitumor responses and tumor destruction.
The blockade of immune checkpoints unleashes the potential of the antitumor immune response in a fashion that is transforming cancer therapeutics. Checkpoint-blocking antibodies have lately demonstrated impressive clinical benefits and long-term survival, even for end-stage patients, raising hopes that this novel approach will lead to effective therapeutic strategies and valuable additions in the fight against cancer.