Cancer immunotherapies have demonstrated clinical efficacy in different types of cancer. However, many tumors show significant resistance to checkpoint blockade presumably due to insufficient rectification of the immunosuppressive tumor microenvironment (TME) and the limited reinvigoration of antitumor immunity.
Teon takes a unique approach to improve the TME and reinvigorate anticancer immunity:
Targeting key GPCRs and enzymes in the TME that are upregulated on immune cells and cancer cells
Developing a synergistic pipeline of first-in-class and best-in-class compounds across the TME metabolic signaling pathways
TME (Tumor Microenvironment)
Teon can antagonize metabolic pathways that suppress antitumor immunity and promote cancer cell proliferation
The immunosuppressive state of the TME is regulated by the metabolic activity of cancer cells. Rapidly proliferating cancer cells require high levels of energy and therefore metabolic reprogramming has emerged as a key feature for cancer survival under hypoxia, stress and limited nutrient availability. Metabolic reprogramming generates large amount of metabolites that not only alter the TME, adversely affect the survival and function of immune cells but also directly stimulate cancer cell proliferation. The common feature of this metabolic reprogramming is that cancer cells switch their glucose metabolism toward “aerobic glycolysis” (Warburg effect), thus decreasing glucose availability and increasing lactic acid in the TME. The hypoxic, glucose-deprived and lactic acid-enriched TME impairs T cell function and thus antitumor immune response. Metabolic stress leads to the release of the danger signal molecule ATP into the TME. ATP is rapidly converted to adenosine, which activates adenosine receptors (A2A and A2B) on immune cells and cancer cells and consequently inhibits immune function and promotes cancer cell survival. Aberrant lipogenesis is another key feature of metabolic reprogramming in cancer cells. While lipids provide additional energy required by proliferating tumor cells, their metabolites, such as prostaglandin E2 (PGE2), can dampen the function of immune cells through activation of EP4 receptors.