Life Sciences & Biotechnology
Title : | Evaluating pH-sensitization of immunotherapy treatment regimens with non-invasive Chemical Exchange Saturation Transfer (CEST) Magnetic Resonance Imaging (MRI) |
Area of research : | Life Sciences & Biotechnology |
Principal Investigator : | Dr. Sanhita Sinharay, Indian Institute Of Science, Bangalore, Karnataka |
Timeline Start Year : | 2022 |
Timeline End Year : | 2025 |
Contact info : | sanhitas@iisc.ac.in |
Equipments : | HPLC |
Details
Executive Summary : | Immunotherapy has proven successful in treating melanoma and lymphoma, but it has not been successful in other cancers, particularly solid tumors. Extracellular acidosis in the tumor microenvironment is a leading cause of resistance to immunotherapy. This is due to upregulated aerobic glycolysis, which produces excess lactic acid in tumor cells. A potential solution could be to raise the extracellular tumour pH and sensitize the tumor to the therapy. The researchers propose using Chemical Exchange Saturation Transfer (CEST) Magnetic Resonance Imaging (MRI) to monitor tumour acidosis during pH-sensitizer treatment and immunotherapy. This quantitative and non-invasive in vivo assessment of extracellular tumour pH (pHe) has two major objectives: identifying high acidosis tumors before treatment initiation and monitoring the decrease in acidosis during pH-sensitizer treatment. The major advances will be the design and synthesis of a smart and responsive non-metallic CEST MRI agent and its validation in a 3T Siemens MRI machine. The key innovation is the design of a smart CEST MRI contrast agent that can deliver a pH-responsive and pH-unresponsive signal from the same moiety, enabling concentration-independent tumor pHe assessment. This combination of using an inhibitor of a pH-exchanger/regulator for reducing tumor acidosis and longitudinally monitoring tumor pHe in a non-invasive manner with CEST MRI can provide a powerful personalized medicine paradigm for clinical application. |
Total Budget (INR): | 59,98,696 |
Organizations involved