Glyco-Immune Checkpoints are a significant and previously unappreciated axis of immunosuppression in cancer. Glyco-Immune Checkpoint receptors function as “off switches” on immune cells, inhibiting immune activity after sensing specific glycan patterns. These receptors normally play a functional role in regulating immune cell activation, especially in helping the immune system distinguish between self and non-self. Tumors exploit this hard-wired system by evolving in such a way that glycans on their cell surfaces activate the receptors. This allows tumors to turn off immune cells, preventing them from killing cancer cells. Glyco-Immune Checkpoints are unique in that they are expressed on a broad range of innate and adaptive immune cell types, so their manipulation by cancer results in a wide-ranging and comprehensive suppression of the immune system. This axis of immunosuppression has been overlooked relative to other strategies in immuno-oncology due to the complexity of glycoscience, and, until recently, the lack of scientific tools to demonstrate its relevance to the immune response.
Glyco-Immune Checkpoints can be targeted by either blocking the receptors on immune cells that sense the tumor glycans, or by impairing the glycans on the surface of cancer cells. Palleon has developed two platforms, CONVERGENCE and EAGLE to pursue each approach.
Palleon’s CONVERGENCE platform enables the efficient development of drugs that target Glyco-Immune Checkpoint receptors on immune cells. One of the key challenges for drug development in this area is the significant differences that exist between human and mouse biology. The Siglecs are the largest and most important family of Glyco-Immune Checkpoint receptors. Human beings have ten Siglecs unique to humans, while mice have five Siglecs unique to mice. Consequently, traditional mouse models cannot be used effectively to target this pathway. Palleon’s CONVERGENCE platform addresses these human-mouse differences by integrating human biology into every step of the drug development process, including target validation, in vitro models, in vivo models and translational research. In this manner, the CONVERGENCE platform enables Palleon to overcome human-mouse differences and target the Siglecs as a new class of receptors for antibody therapies
Palleon’s EAGLE platform enables the efficient development of drugs that target Glyco-Immune Checkpoint ligands, the glycans on the surface of cancer cells. The critical challenge in this area arises from the complexity, heterogeneity and rapidly evolving nature of tumor glycans. Palleon’s EAGLE platform uniquely addresses this challenge by impairing the glycans on tumor cells in a manner that overcomes the intricacy and evolution of these structures. Tumors are thereby prevented from exploiting Glyco-Immune Checkpoint receptors, and the immune system can effectively kill the cancer cells.
Palleon’s two platforms, CONVERGENCE and EAGLE, will facilitate the development of therapeutics that address a wide range of cancer patient populations.
Palleon has several cancer drug discovery programs underway. Beyond oncology, other important areas where Glyco-Immune Checkpoints may play a role include infectious diseases, neurodegeneration, inflammation and fibrosis.