Researchers from Cyncado Therapeutics say that TT-4 monotherapy outperforms anti-PD-1 checkpoint inhibitors in treating mesothelioma, and that combining the two improves anti-tumor activity and increased T-cell infiltration even more. The group will be presenting details of its research at the upcoming AACR-NCI-EORTC International Conference to be held in Boston, Massachusetts, this coming weekend.
Researchers Focus on Adora2B Receptor Inhibitor
ADORA2B, or Adenosine A2B receptor, is a G protein-coupled receptor implicated in tumor progression and poor prognosis in various cancers, including mesothelioma. Cyncado Therapeutics administered their experimental drug TT-4, which blocks ADORA 2B, to mesothelioma cells and demonstrated that it reduced the levels of PD-L1, which is another agent that mesothelioma cells use to fend off the immune system.
Much of immunotherapy use in treating mesothelioma has focused on anti-PD-1treatments, but the scientists found that TT-4 outperformed anti-PD-1 checkpoint inhibitor treatment, and that combining the two demonstrated significantly greater anti-tumor activity and increased T-cell infiltration compared to either agent alone. TT-4 appears to work through a twofold mechanism that involves direct effects on cancer cells as well as enhanced immune system activity against tumors.
Mesothelioma Drug Development Advances Toward Human Clinical Trials
Dr. Rob Kramer, Chief Scientific Officer at Cyncado Therapeutics, said, “In vitro, we see a direct anti-tumor effect in both epithelial and non-epithelial mesothelioma cells, with PD-L1 falling in step with reduced pCREB. In vivo, TT-4 is active as a single agent and adds benefit with anti-PD-1, clear signals that are guiding our clinical strategy.”
The mesothelioma treatment holds exciting potential, but the results to date have been limited to a single cell line and an in vivo model. To establish human safety, dosing, and effectiveness, the company anticipates beginning human mesothelioma patient dosing in clinical trials beginning in the first quarter of 2026. The research represents a collaboration including partners from the University of L’Aquila, Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, St. James’s Hospital Dublin, and Cyncado Therapeutics.
If you or someone you love has been diagnosed with mesothelioma, this research represents hope for more effective treatments and extended survival. For information on resources available to you, contact the Patient Advocates at Mesothelioma.net today at 1-800-692-8608.