Malignant mesothelioma is among the most challenging cancers to treat. The rare form of cancer, caused by exposure to asbestos, has proven resistant to chemotherapy, and as each new therapeutic has been introduced its tumors have revealed a new defense. In response to the use of checkpoint inhibitors and CAR-T protocols, mesothelioma cells secrete transforming growth factor beta, or TGF-β, into their microenvironment. This multifunctional cytokine acts as part of the tumors’ immune evasion mechanism, but now a California immune-oncology company is initiating a Phase 2 Trial for OT-101, which inhibits TGF-β and its effects.
Phase 2 Clinical Study Includes Mesothelioma, Glioblastoma, and Other Cancers
Results from initial studies of OT-101 have been promising, and Oncotelic Therapeutics, Inc. is now moving on to a Phase 2 trial that will involve patients with malignant mesothelioma, glioblastoma, lung, and colorectal cancers. The company’s oncology program depends heavily on artificial intelligence and responds to local tumoral secretion of TGF-β that suppresses the clinical activity of checkpoint inhibitors and CAR-T. The drug has also shown promise in the fight against COVID-19, where TGF-β has suppressed the effectiveness of vaccines. The trial will not only test the effectiveness of the drug, but also be used to identify predictive biomarkers for TGF-β.
Discussing the goal of the test and its impact on mesothelioma, Dr. Anthony Maida, Chief Clinical Office – Translational Medicine for the company said, “This is the first of a series of planned clinical trials in patients with various solid tumors evaluating clinical benefit while also assessing a host of parameters associated with changes in the tumor microenvironment, including but not limited to T-cell infiltration, expression of various cytokines, and phenotypic and functionality changes pre-therapy versus post-therapy.”
TGF-β Secreted by Mesothelioma Cells Offsets the Impact of Immunotherapy
Upon learning of the negative impact that TGF-β released by mesothelioma has on the effectiveness of immunotherapy, researchers are working to counter the tumors’ defense. Says Dr. Vuong Trieu, CEO and Chairman of Oncotelic, “The groundwork laid down by OT-101/IL-2 and OT-101/PD-1 will serve as the foundation for future strategic alliances for OT-101/CAR-T and OT-101/Vaccines. CAR T-cell therapy, in which a patient’s immune T cells are modified so they will bind to cancer cells and kill them, has been shown to benefit greatly from TGF-β inhibition in early clinical testing.”
If you or someone you love has been diagnosed with malignant mesothelioma, this type of innovative research gives real reason for hope. For access to state-of-the-art research, contact the Patient Advocates at Mesothelioma.net at 1-800-692-8608.
