Immune checkpoints are negative regulators of the immune system, that play critical roles in maintaining self-tolerance, preventing autoimmunity and protecting tissues from immune collateral damage. These immune checkpoints are often “hijacked” by tumors to restrain the ability of the immune system to mount an effective anti-tumor response. Blocking immune checkpoints is thus a promising approach for activating anti-tumor immunity.
Indeed, recently, the antibody-based drugs blocking the immune checkpoints CTLA4 and PD-1 emerged as “game changers” in cancer therapy, leading to durable clinical responses even in patients with advanced cancer. The breakthrough successes in melanoma, lung and kidney cancers provided a therapeutic validation for this approach and formed the foundation for a new era of cancer immunotherapy.
Despite the success of CTLA4 and PD-1 blockers, many patients do not respond to these treatments. Furthermore, clinical benefit is still limited to a small subset of cancer indications, and only a minority achieves the promise of long-term survival. It is therefore clear there are additional immune evasion mechanisms mediated by other immune checkpoint proteins.
The activity of the immune system is mostly regulated by immune cells called T cells. One protein family which is responsible for regulating immune cells, including T cells, is the B7/CD28 family of co-stimulatory and co-inhibitory receptors and ligands. Naïve T cells are initially activated by antigens derived from invading pathogens or from malfunctioning cells, such as cancer cells. The magnitude and efficacy of the immune response is determined by a delicate balance between co-stimulatory and co-inhibitory signals. Cancer cells exploit this regulatory mechanism by continuously inducing co-inhibitory signals (immune checkpoints) to evade immune destruction. Therefore, the ultimate goal of cancer immunotherapy is to enable the immune system to detect cancerous cells, destroy them and prevent further tumor development.
Compugen discovered several novel immune checkpoint candidates with the potential to become first-in-class drug targets. This sets us apart from many companies in this field that are pursuing the same few known immune checkpoint targets. Targeting novel immune checkpoints can potentially benefit unresponsive patient populations and address additional cancer indications. This provides us with a very meaningful competitive advantage both for monotherapy and for combination therapy.