Researchers from Rice University and Baylor College of Medicine developed a new treatment that can eliminate advanced stage mesothelioma tumors in mice within days. The breakthrough treatment used Rice’s cytokine drug factory implants with a checkpoint inhibitor drug. This combination is showing great potential in mesothelioma preclinical trials. The treatment involves tiny drug producing beads, each no bigger than a pinhead, implanted near tumors. The beads release high doses of interleukin-2 (IL-2), a natural protein that stimulates white blood cells to attack cancer. By continuously supplying IL-2, the therapy enhances the immune system’s ability to recognize and destroy cancerous cells. A recent study published in Clinical Cancer Research showcases the success of the approach, showing how effective the technology can be.
The goal of researchers was to develop a platform therapy that could be used for multiple types of immune system disorders and cancers. The cytokine factories are comprised of tiny alginate beads packed with tens of thousands of genetically engineered cells that produce IL-2. The beads are only 1.5 millimeters across, meaning they can be implanted through minimally invasive surgery. Implanting them near tumors ensures a steady localized IL-2 supply without systemic toxicity.
In the case of the mesothelioma study, the beads were implanted by researchers directly beside the tumors within the pleura, the membrane that surrounds the lungs. This helped to maximize the immune response while also limiting side effects often seen with traditional cancer therapies. Mesothelioma is a very aggressive cancer that is hard to remove completely through surgery. There are usually residual cancer cells or even tumors left behind. Localized immunotherapy treatments-delivering high doses of immunotherapy directly to the pleural space, is a very attractive way to treat the disease.
Researchers started to look into treating mesothelioma with the beads because of other successful research that used the beads on ovarian cancer in animal tests. The tests were collaborated on at the University of Texas MD Anderson Cancer Center, showing that IL-2 producing beads could eliminate advanced stage ovarian cancer and colorectal cancer tumors in mice in less than a week. Researchers were impressed with the research and wanted to apply it to mesothelioma.
Mesothelioma is a cancer that occurs in tissue linings that surround and protect internal organs including the lungs (pleural), abdomen (peritoneal), heart (pericardial), and testicles (testicular). Around 80 percent of cases are linked to heavy and prolonged asbestos exposure. Immunotherapy, especially checkpoint inhibitors, has shown some success when treating this cancer. Checkpoint inhibitors do not directly kill cancer cells. Instead, they train the immune system to recognize and kill cancer cells.
In the mesothelioma study, the drug factory implants were tested alone and as a combination with checkpoint inhibitors that target the PD-1 protein. When used by themselves, the implants killed tumors in over 50 percent of the treated animals. In the group that was treated with the drug factory implants and the PD-1 checkpoint inhibitor, tumors were completely destroyed in all of the mice.
Mesothelioma tumors are very hard to treat in mice, just like in humans. Findings show that the regional delivery of the immunotherapy particles to mice with mesothelioma produces a very robust treatment response. Researchers have not seen the eradication of mesothelioma tumors like this in mice before. The results from the study also reveal that combining IL-2 producing implants with anti-PD-1 checkpoint inhibitors might effectively train memory T cells. These cells could potentially reactivate if the cancer returns. A spinout company known as Avenge Bio has received FDA clearance to use the IL-2 cytokine factories to treat ovarian cancer patients. They expect to start treating ovarian cancer patients within the next couple of months.
The promising data from this study has laid the groundwork to perform a second clinical trial aimed at patients with mesothelioma and other lung cancers with pleural metastasis. Meetings with the FDA have taken place. This technology is also being applied to the heart and researchers have gotten a grant from the American Heart Association to see how the cytokine implants perform when trying to heal heart injuries caused by heart attacks.
