Life-changing treatment eradicates advanced-stage cancers in 6 days

Researchers at Rice University and Baylor College of Medicine have found a new combination treatment that can eradicate advanced-stage mesothelioma tumors in mice in just a few days. The treatment combines Rice’s cytokine “drug factory” implants and a checkpoint inhibitor drug.

The study, published in Clinical Cancer Research, demonstrates the success of the drug-factory technology invented in the lab of Rice bioengineer Omid Veiseh.

Mesothelioma is a type of cancer that occurs in the tissue linings that surround and protect internal organs. It is usually caused by prolonged exposure to asbestos, which leads to damage and changes in the cells that line the lungs, abdomen, or heart. It is an aggressive malignancy that is very hard to treat completely by surgical resection. In other words, there is often residual disease that is left behind.

The treatment of this residual disease with local immunotherapy – the local delivery of relatively high doses of immunotherapy to that pleural space – is a very attractive way to treat this disease.

Immunotherapy with drugs called checkpoint inhibitors has met with some success in treating mesothelioma. Checkpoint inhibitors don’t kill cancer directly but rather by training the immune system to recognize and destroy cancer cells.

The researchers administered the drug-producing beads, which are no larger than the head of a pin, next to tumors where they could produce continuous, high doses of interleukin-2 (IL-2), a natural compound that activates white blood cells to fight cancer.

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The cytokine factories consist of alginate beads loaded with tens of thousands of cells that are genetically engineered to produce natural IL-2, one of two cytokines the FDA has approved for treatment of cancer.

The factories are just 1.5 millimeters wide and can be implanted with minimally invasive surgery to deliver high doses of IL-2 directly to tumors.

In the mesothelioma study, the 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 researchers tested Veiseh’s drug factory implants both by themselves and in combination with a checkpoint inhibitor that targeted the PD-1 protein. They found the drug factory implants eliminated tumors in more than 50% of the treated animals when used by themselves.

Tumors were destroyed completely in all seven mice that were treated with both the drug factory implants and PD-1 checkpoint inhibitor.

“It’s very hard to treat mesothelioma tumors in mice, like it is in human beings,” said Dr. Bryan Burt, professor and chief of Baylor’s Division of Thoracic Surgery in the Michael E. DeBakey Department of Surgery.

“And 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.”

The results of the study also suggest that the combination of IL-2-producing implants and anti-PD-1 checkpoint inhibitors could be effective at training “memory T cells” that can reactivate the immune system to fight mesothelioma if it recurs.

“From the beginning, our objective was to develop a platform therapy that can be used for multiple different types of immune system disorders or different types of cancers,” said Rice graduate student Amanda Nash, who spent several years developing the implant technology with study co-lead author Samira Aghlara-Fotovat, a fellow student in Veiseh’s lab.

Veiseh said the mesothelioma study began when Burt and Baylor surgeon and associate professor Dr. Ravi Ghanta heard about the early results of ovarian cancer animal tests Veiseh’s team was conducting with collaborators at the University of Texas MD Anderson Cancer Center.

In March, Veiseh and MD Anderson collaborators published a study showing IL-2-producing beads could eradicate advanced-stage ovarian and colorectal tumors in mice in less than a week.

The team was excited to test their technology on mesothelioma, a cancer that is notoriously difficult to treat. The disease affects the lining of the lungs and is primarily caused by prolonged exposure to asbestos. There are currently no known cures for mesothelioma, and treatment options are limited.

The Rice-Baylor team used checkpoint inhibitors, a type of drug that targets the PD-1 protein, in combination with the drug factory implants. The checkpoint inhibitors help to train the immune system to recognize and destroy cancer cells.

When used alone, the implants eliminated tumors in over 50% of the treated mice. However, when used in combination with the PD-1 checkpoint inhibitors, all seven mice had their tumors completely destroyed.

The study showed that the combination of IL-2-producing implants and anti-PD-1 checkpoint inhibitors could be effective at training "memory T cells." These cells could help reactivate the immune system to fight mesothelioma if it were to recur.

Dr. Bryan Burt, a professor and chief of Baylor's Division of Thoracic Surgery in the Michael E. DeBakey Department of Surgery, said the study's results were promising. "It's very hard to treat mesothelioma tumors in mice, like it is in human beings," he said.

"And 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."

Veiseh said the results of the study were exciting because they suggested that the drug factory implants could be used to treat other types of cancer as well. "From the beginning, our objective was to develop a platform therapy that can be used for multiple different types of immune system disorders or different types of cancers," he said.

The technology behind the cytokine factories consists of alginate beads loaded with tens of thousands of cells that are genetically engineered to produce natural IL-2. The beads are just 1.5 millimeters wide and can be implanted with minimally invasive surgery to deliver high doses of IL-2 directly to tumors.

Amanda Nash, a Rice graduate student who spent several years developing the implant technology with study co-lead author Samira Aghlara-Fotovat, said the technology had the potential to revolutionize cancer treatment.

"We have a spinout company, Avenge Bio, that recently received clearance from the FDA to treat ovarian cancer patients, and in the next couple of months they expect to begin treating patients with these IL-2 cytokine factories," she said.

The preclinical data reported in the latest manuscript helped justify initiating a second clinical trial for patients suffering from mesothelioma and other lung cancers with pleural metastasis. Veiseh said the team had held meetings with the FDA and expected to initiate a second trial for this patient population in the latter half of 2023.

The potential impact of this technology on cancer treatment is significant. By using genetically engineered cells to produce natural compounds that activate white blood cells to fight cancer, the cytokine factories have the potential to transform cancer treatment.

Although the technology is still in the early stages of development, the results of this study suggest that it could be a promising approach to treating mesothelioma and other types of cancer.

Note: Materials provided above by The Brighter Side of News. Content may be edited for style and length.

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