A new anti-CD26 monoclonal antibody, YS110, may be a promising therapeutic approach for patients with malignant mesothelioma (MM), according to researchers at the Graduate School of Medicine, Juntendo University, in Japan.
The study, “Development of New Therapy for Malignant Mesothelioma Based on CD26 Molecule,” published in the Japanese Gan To Kagaku Ryoho journal of cancer and chemotherapy, described the beneficial results in a MM mouse model.
CD26 is a surface molecule appearing to be involved in mesothelioma tumor growth, migration, and survival. Approximately 80 percent of mesothelioma patients have tumors that express the molecule in epithelial mesothelioma cells. But researchers found that normal mesothelioma cells do not express CD26, which makes it a promising target for future therapeutic approaches.
In fact, researchers discovered that a biologically active CD26 monoclonal antibody had promising anti-tumor effects in mice bearing a human mesothelioma tumor. The agent, YS110, disrupted the normal cell cycle of the malignant mesothelioma cells, which caused them to enter into apoptosis (cell death). Surprisingly, YS110 was able to reduce mesothelioma tumor growth by 20 percent in 48 hours.
The researchers also reported that YS110 worked even better when administered in combination with the standard of care treatment for mesothelioma patients — Alimta (pemetrexed).
Recently, a Phase 1 study using YS110 in humans was performed by French researchers. The study, “First-in-human phase I administration of YS110, a monoclonal antibody directed against the CD26 immunostimulatory molecule in advanced cancer patients,” enrolled 34 patients with advanced/refractory CD26-expressing cancers, including 23 with mesothelioma and 10 with renal carcinoma who received escalating doses of YS110.
The study, presented during the American Society of Clinical Oncology 2015 meeting, showed that the humanized anti-CD26 therapy was well tolerated by the patients and there was evidence of activity of YS110, as assessed by prolonged stabilization in more than half of patients.
Japanese researchers intend to start a Phase 1 clinical trial in Japan in the very near future. The team wants to assess how the drug performs in patients with advanced inoperable mesothelioma or in heavily treated mesothelioma patients.