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Cytokine Factories to Treat Pleural and Peritoneal Mesothelioma

Published: February 10, 2023

A new study from Rice University in Houston is showing promising results for mesothelioma. It utilizes the immune system to fight cancer cells. The protein that is being studied is interleukin 2 (IL2), which is a protein that regulates white blood cells through the use of cytokines, a cell signal that affects other cells. When the researchers studied the effects on mice, the tumor burden fell around 80 percent. The authors of the study believe that research on IL2 treatments needs to continue, which could potentially lead to a new standard mesothelioma therapy.

One way to fight tumors is to use cytokine factories. They are delivery systems that make naturally occurring immune cells fight cancer cells. The factories are made up of thousands of drug producing cells in a microscopic bead. The study utilized mice to determine efficacy of the treatment. Mesothelioma is a fast acting disease, so treatment options also need to be fast acting to best treat it. The IL2 cytokine factories helped eradicate aggressive mesothelioma tumors and protected from tumor recurrence. Nearly 90 percent of the mice treated with 1.5 μg survived twice as long as those who did not receive treatment. After one week, 19 of 26 mice had tumor reduction greater than 45 percent, even with varying doses. More than 91 percent of the mice treated with 2.5 μg or more had a larger than 75 percent reduction in tumor burden within a week. All the mice treated with 5 μg had a 90 percent decrease in tumor burden.

IL2 is critical in activating the immune system to fight infection and disease and is the only therapy involving cytokines to be approved by the FDA. When administered, the body released a large amount of T cells. The immune cells destroy tumor cells and create antibodies to help prevent cancer recurrence. IL2 cytokine factories are a great option for people who have not responded to other immunotherapy treatments. The treatment was easily controlled by regulating the density of engineered cells in capsules. When the cell concentration increased, IL2 also increased. The dosage was controllable without any loss of cell viability. During the course of treatment, researchers noticed that it was tolerated very well. The treatment also helped improve anti-PD1 therapy.

The IL2 treatment could be an effective therapy for both pleural and peritoneal mesothelioma patients. The treatment was studied on peritoneal mesothelioma by implanting the cytokine factory in the peritoneal space of mice. IL2 cytokine factories do not need much access to the target site to be effective. When tested for pleural mesothelioma, the researchers noticed that the local concentration (at treatment site) was 100 times greater than the systemic concentration (entire body), meaning there is minimal leaking into the rest of the body, which reduces side effects. Researchers took precautions to test for toxicity in the liver, kidneys, and lungs because this therapy can negatively affect these organs. There were no cellular changes in these organs after the study was finished. Insulin and glucose levels were also not affected.

Based on data from the study, researchers believe that an extended regimen of this therapy would not negatively affect patients. Once the treatment was completed, the capsules did not continue delivering cytokines. The dosage peaked at day four and reduced as scar tissue formed on the capsule. Researchers were able to extract 80 percent of the capsules after the study, which shows the factories are stable at body temperatures.

Amanda M. Nash et al., “Activation of Adaptive and Innate Immune Cells via Localized IL2 Cytokine Factories Eradicates Mesothelioma Tumors” Translational Cacer Mechanisms and Therapy (December 1, 2022). [Link]
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