Inhibition of Acid Sensing by Allosteric Modulation of GPR65 Normalises Gene Expression in Primary Macrophages, Increases Natural Killer Cell Infiltration in Subcutaneous MC38 Tumors, and Restricts Tumor Growth

Time: 3:45 pm
day: Day Two

Details:

  • Displaying how high frequencies of Tumor-Associated Macrophages (TAMs) are associated with poor patient prognosis
    • Leveraging the fact acidic conditions of the tumor microenvironment suppress macrophage immune function and support a pro-tumor TAM state
  • Demonstrating how TAMs sense low pH through G-Protein Coupled Receptor 65 (GPR65)
  • Utilizing Pathios compounds to inhibit GPR65 sensing of pH in vitro with excellent potencies, resulting in profound gene expression changes, and demonstrate therapeutic benefit in the MC38 Tumor Growth Inhibition model in vivo, elevating the frequency of tumor-infiltrating Natural Killer cells

Speakers: