'Drug Factory' Implants Eliminate Tumors In Mice, Setting up Human Trials

Research with Mouse

Scientists found that combining cytokine drug factory implants with PD-1 protein targeting checkpoint inhibitors can eliminate advanced-stage mesothelioma tumors in mouse models - laying the groundwork for human trials. 

Researchers from Rice University and Baylor College of Medicine tested Rice bioengineer Omid Veiseh's drug factory technology by itself and in combination with an anti-PD-1 checkpoint inhibitor on mice with mesothelioma. This is a type of cancer that occurs in tissue linings surrounding and protecting internal organs.

They found that the drug factory implants, invented in Veiseh's lab with Baylor professors and surgeons Dr. Ravi Ghanta and Dr. Bryan Burt, were able to eliminate tumors in over 50 percent of the animals. The tumors were completely destroyed in seven of the mice that were given both the implants and the PD-1 checkpoint inhibitor.

The drug-producing beads had the ability to produce continuous high doses of interleukin-2 when placed next to tumors. IL-2 is a natural compound that activates white blood cells to combat cancer cells. It is also one of two cytokines that the FDA has approved to be used for cancer treatment.

The cytokine factories consist of alginate beads that contain tens of thousands of these genetically engineered cells. For the Rice-Baylor study, the beads were positioned beside tumors and inside the pleura, or the thin tissue layer covering the lungs and lining the chest's interior wall.

"What our data show is that delivery of these immunotherapy particles, regionally, to these mice who have mesothelioma, has very provocative and very effective treatment responses. In fact, I've not seen these mesothelioma tumors in mice be eradicated, with such efficacy, as we have in this mouse model," Dr. Bryan Burt, a professor and chief of Baylor's division of thoracic surgery in the Michael E. DeBakey department of surgery, said in a statement.

Aside from establishing the potential to eliminate tumors, the results also suggest that combining anti-PD-1 checkpoint inhibitors with IL-2-producing implants may effectively train memory T cells that can reactivate the immune system should the mesothelioma recur. The FDA granted Rice's spinout company, Avenge Bio, clearance to treat ovarian cancer patients, Veiseh said.

"In the next couple of months, they expect to begin treating patients with these IL-2 cytokine factories," he stated. "The preclinical data reported in our latest manuscript helped justify initiating a second clinical trial for patients suffering from mesothelioma and other lung cancers with pleural metastasis." The team has held meetings with the FDA and expects to initiate a second trial for this patient population in the latter half of 2023, Veiseh said. 

Details of the study are published in Clinical Cancer Research. It is funded by the Cancer Prevention Research Institute of Texas, the National Science Foundation and the National Institutes of Health. The American Heart Association has also given Drs. Veiseh and Ghanta a grant to evaluate cytokine implants for healing heart injuries caused by heart attacks.

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