|February 16, 2022
|Developing Imaging Biomarkers for Immunotherapy Resistance In Vivo
|The University of Texas M.D. Anderson Cancer Center
|Principal Investigator/Program Director
Despite remarkable progress in immunotherapy, definitive biomarkers which can accurately predict clinical response to immunotherapy are still lacking. Resistance to immunotherapy can be largely attributed to extracellular acidity in the tumor microenvironment. We propose to reduce the acidity to improve the response to immunotherapy. We propose to inhibit Vacuolar ATPase that pumps acid out of the tumor cell; Monocarboxylate Transporter 1 that secretes lactic acid into the tumor microenvironment; and Carbonic Anhydrase IX that neutralizes intracellular acids and causes extracellular acidity. We refer to the use of one or more of these inhibitors as "pH-sensitizers" for immunotherapy. We will...