Implantable “Drug Factory” Eradicates Mesothelioma in Mice When Combined with a Checkpoint Inhibitor

Mesothelioma refers to any cancer that occurs in the tissue linings that surround and protect internal organs, while malignant pleural mesothelioma (MPM) is the most common type. It is a rare but extremely aggressive cancer that is difficult to treat even with surgical intervention. However, by combining a checkpoint inhibitor with a newly developed cytokine “drug factory” implant, scientists have recently succeeded in eradicating advanced mesothelioma tumors in mice in just a few days, providing a promising opportunity to develop future therapies.

Related Article: FDA Approves Treatment for Aggressive Form of Mesothelioma After Sixteen Long Years

A Promising Candidate to Treat Aggressive Lung Cancer

The new mesothelioma study is a joint effort between Baylor College of Medicine and the laboratory of Prof. Omid Veiseh, Assistant Professor of Bioengineering at Rice University, and the results were published online last month in the journal Clinical Cancer Research. The implants used are the latest in a series of successful drug factory applications Veiseh’s team is developing. After releasing early results from a collaborative animal trial with the University of Texas using a cytokine factory to treat ovarian cancer this March, Veiseh’s team has been working with the Baylor College of Medicine team on a study of mesothelioma treatment since then because of the impressive preclinical data. 

The cytokine factories developed by Veiseh’s team consist of alginate beads, each only 1.5 millimeters wide, loaded with tens of thousands of cells genetically engineered to produce interleukin-2 (IL-2), one of two FDA-approved cytokines to treat cancer. Implanted with minimally invasive surgery, the cytokine factories continuously deliver high doses of IL-2 to the tumor site, stimulating an immune response to fight against cancer. 

In the mesothelioma study, the alginate beads were placed beside tumors and inside the thin layer of tissue known as the pleura, which covers the lungs and lines the interior wall of the chest. The results confirmed that Veiseh’s cytokine factories helped eliminate the tumor, and the treatment was even more effective when combined with a checkpoint inhibitor targeting PD-1 protein.

When used alone, the cytokine factory implants eliminated tumors in more than 50% of the treated animals. Combining cytokine factory implants and PD-1 checkpoint inhibitors eradicated tumors in all seven mice that received the blended therapy. The results also showed that the combination of the two effectively trained memory T cells, which could restimulate the immune system to fight mesothelioma even in the event of relapse.

Video: Cancer fighting ‘drug factories’ show promise in fighting mesothelioma 

Cytokine Factories’ Potential in a Variety of Applications

Bryan Burt, Professor and Chief of the Division of Thoracic Surgery at Baylor College of Medicine, explained that treating mesothelioma in mice, as in humans, is very difficult, and the data showed that the cytokine factory was very effective in mice with mesothelioma. He was amazed by how efficiently the therapy eradicated tumors in mice in the study model.

According to Samira Aghlara-Fotovat, a member of Veiseh’s laboratory and another author of this study, the team’s goal from the beginning was to develop a therapeutic platform that could apply to many different types of immune system diseases or various types of cancer. 

Avenge Bio, a start-up company formed by Veiseh’s team is developing the LOCOcyte immunotherapy platform, which utilizes alginate capsules loaded with engineered cells that secrete IL-2. The platform recently received clearance from the FDA to treat ovarian cancer patients, and the team expects to begin human clinical trials with these IL-2 cytokine factories in the coming months. In addition to ongoing research on treatments for mesothelioma and other pleural metastatic lung cancers, the research team has received funding from the American Heart Association to explore the therapeutic potential of drug factories for treating cardiac damage caused by a heart attack. 

Written by Nana Ho, translated by Richard Chau

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