Compugen predictive discovery capabilities for cancer immunotherapy are focused on novel B7/CD28 like immune checkpoints and other immunomodulatory protein candidates.
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, which has been proven clinically by the success of antibody antagonists of the T cell checkpoints CTLA4, PD-1, and PD-L1.
1. T cell receptor activation via co-stimulation (shown in green) is required for initiating an effective immune response.
2. Activated T cells express co-inhibitory receptors on the cell surface, limiting collateral tissue damage.
3. Cancer cells can use immune checkpoint signaling pathways to restrain effective anti-tumor immune responses, thereby evading destruction.
4. The blockade of co-inhibitory ligands present on the cancer cells or their counterpart receptor in the infiltrating T cells can unleash anti-tumor immune responses.
Compugen discovered several novel immune checkpoint candidates that serve as the basis for 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 checkpoint pathways s can potentially benefit unresponsive patient populations and address additional cancer indications. This provides us with a meaningful competitive advantage both for monotherapy and for combination therapy.
Compugen has extended its predictive discovery capabilities for cancer immunotherapy beyond the successful initial focus on immune checkpoints, and through the application of additional computational platforms has discovered various novel immunomodulatory protein candidates.
Immunomodulatory proteins are proteins capable of modifying or regulating one or more immune functions. Immune checkpoints, including inhibitory receptors and ligands, are one type of immune modulators.
Myeloid biology is a critical component of immune suppression. The myeloid lineage of the immune system includes macrophages, immune cells that are highly immune suppressive in the tumor microenvironment, and that can affect the anti-tumor immune response via multiple mechanisms of action. With the aim of complementing and expanding the patient population responsive to checkpoints inhibitors, blocking myeloid targets may serve as the next wave of cancer immunotherapies. The Company’s LINKS Platform was enhanced to discover new myeloid targets within the tumor microenvironment. Myeloid CGEN-target candidates have been identified within the tumor microenvironment of multiple cancers and are pursued by the Company.
Key mechanisms of action for Compugen’s myeloid target candidates