New Mesothelin-targeting Combo Shows Promise Against Cancer Cells in Mice Studies

New Mesothelin-targeting Combo Shows Promise Against Cancer Cells in Mice Studies

An antibody and drug combination by Bayer that targets the molecule mesothelin was found to have potent anti-cancer effects on lab-grown cells and animal models of malignant mesothelioma, according to a new study.

Mesothelin is found in malignant mesothelioma tumors and a number of other cancer types. Researchers do not know what it does in healthy people, and it is only found in relatively small amounts outside tumors. That makes it an attractive target for cancer treatment development.

In lab-grown cells, the treatment — called anetumab ravtansine, or BAY 94-9343 — selectively bound mesothelin, and was then taken up by the cancer cells, according to the study, “Anetumab Ravtansine: A Novel Mesothelin-Targeting Antibody–Drug Conjugate Cures Tumors with Heterogeneous Target Expression Favored by Bystander Effect.”

Researchers from Bayer HealthCare Pharmaceuticals confirmed that the compound accumulated in the cells, which is important because many cancer cells can expel unwanted molecules.

The report was published in the journal Molecular Cancer Therapeutics.

Researchers also found that BAY 94-9343 was toxic to cells in dishes, and it hampered cancer growth in animal models of mesothelioma, including mice growing tumors directly derived from patients.

The treatment only bound to tumor cells with mesothelin on the surface, but the team noted that it induced what is known as a “bystander effect.” In that process, targeted cells send out signals that trigger the death of neighboring cells.

BAY 94-9343 had a greater effect in tumors with more mesothelin-expressing cells, but it induced regression in a tumor with only 20% of its cells producing the molecule.

Researchers also compared BAY 94-9343’s effects to those of drugs used as standard mesothelioma care. In mice with mesothelioma, it was more effective in treating tumors than a combination of Platinol (cisplatin) and Alimta (pemetrexed disodium).

A Phase 1 clinical trial (NCT01439152) is evaluating BAY 94-9343’s safety and basic properties in people with advanced solid tumors. A Phase 2 study (NCT02610140) is also underway. It is evaluating the treatment’s efficacy and safety versus vinorelbine (a chemotherapeutic drug) in patients with advanced (stage 4) or metastatic malignant pleural mesothelioma, who are overexpressing mesothelin.

Neither trial is recruiting participants.

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Magdalena is a writer with a passion for bridging the gap between the people performing research, and those who want or need to understand it. She writes about medical science and drug discovery. She holds an MS in Pharmaceutical Bioscience and a PhD — spanning the fields of psychiatry, immunology, and neuropharmacology — from Karolinska Institutet in Sweden.

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