Study: ‘Drug-Factory’ Technology Kills Mesothelioma Tumor Cells in Mice

Tiny, drug-producing beads implanted in the chest cavity could one day provide a powerful platform that would change the way mesothelioma cancer is treated.

In a recent study, researchers from Rice University and the Baylor College of Medicine demonstrated the implants’ impressive effectiveness in mice, raising hopes of a possible breakthrough for this tough-to-treat cancer.

Researchers have already met with the U.S. Food and Drug Administration, and hope to open a clinical trial to begin testing the procedure’s effectiveness on mesothelioma patients by the second half of 2023. Clinical Cancer Research published the latest study Aug. 22.

“There is a lot of work left to be done, but we are definitely excited about the potential and encouraged by the clinical work already done,” Rice University bioengineer Omid Veiseh, whose lab invented the novel technology, told The Mesothelioma Center at Asbestos.com. “This could shift the paradigm [of treatment].”

New Technique Delivers Drugs Directly to Tumors

Drug-producing beads, which are no larger than the head of a pin, can be programmed to produce continuous high doses of genetically engineered interleukin-2, a natural compound that activates white blood cells to fight tumors. Researchers have dubbed the process “drug-factory” technology.

The FDA already has approved the technology with interleukin-2 for a clinical trial involving ovarian cancer. It is scheduled to open near the end of 2022.

For the study of mice with mesothelioma, beads were loaded with thousands of cells and implanted with minimally invasive surgery alongside the tumors and inside the pleural lining that surrounds the lungs.

In the first group, tumor burden was reduced by an average of 80% after only one week of treatment. In more than half of the mice, the implants completely eliminated the tumors.

A second group of mice received a combination treatment of the same interleukin-2 and a checkpoint inhibitor drug, which works by training the immune system to recognize and destroy cancer cells.

In that second group, tumor burden was eliminated in all seven animals, none of which exhibited any recurrence in the following weeks of observation.

“It is very hard to treat mesothelioma tumors in mice, like it is in human beings,” said thoracic surgeon Dr. Bryan Burt, a mesothelioma specialist at Baylor University and the study co-author. “And what our data show is that delivery of these immunotherapy particles, regionally, to these mice that have mesothelioma, has very provocative and very effective treatment responses.”

Continuous Drug Dosage Is Critical

The key, according to authors, is the ability to produce the continuous drug doses alongside the tumors. Immunotherapy drugs by themselves have shown only sporadic effectiveness for patients when given systemically. They have worked especially well only for a small percentage of patients.

“We’ve been working on this technology for a while,” Veiseh said. “This combination does a more effective job of using the immune system to kill the tumors.”

It was Veiseh’s earlier work using his technology with ovarian cancer at Rice University that first caught the attention of Burt and Dr. Ravi Ghanta at Baylor.

“They were really impressed by the preclinical data we had in ovarian cancer,” Veiseh said.  “And they asked the question, ‘Could we actually leverage the same system for mesothelioma?’”

The answer came with the mice model, which is leading to clinical trials.

In addition to showing potential to eliminate tumors, this early study suggests that the drug combination and its delivery method also could be effective at training T cells to reactivate the immune system when mesothelioma recurrence occurs.

“I’ve not seen these mesothelioma tumors in mice be eradicated – with such efficacy – as we have in this mice model,” Burt said. “The local delivery of relatively high doses of immunotherapy to that pleural space is a very attractive way to treat this disease.”

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