Implantable “drug factory” beads destroy tumors in mice within days

Earlier this year, scientists at Rice University demonstrated a highly promising approach to tackling ovarian and colorectal cancer that centered on “drug factory” beads that could be implanted alongside tumors to destroy them in less than a week. By combining this technology with other immunotherapy drugs, the scientists have now explored the potential for this technique to tackle another form of cancer, and achieved very similar results.

The drug factory beads developed by the Rice University team are around the size of a pinhead and are loaded up with tens of thousands of cells genetically engineered to produce interleukin-2 (IL-2). This cytokine naturally activates white blood cells to fight cancer and is approved by the FDA as an immunotherapy treatment for cancer.

By implanting the beads alongside tumors in mouse models of ovarian and colorectal cancer, the drug factories were so effective at continually generating IL-2 that the growths were eradicated in as little as six days. These exciting results caught the eye of another group of researchers working on treatments for mesothelioma, a type of cancer that forms in the tissue lining around internal organs. Around 80 percent of mesothelioma cases are tied to prolonged asbestos exposure.

“I take care of patients who have malignant pleural mesothelioma,” said Dr. Bryan Burt, from Baylor College of Medicine. “This is a very aggressive malignancy of the lining of the lungs. And it’s 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.”

Burt and his colleagues sought to combine the drug factory technology with another form of immunotherapy that has shown some promise in treating mesothelioma, in the form of checkpoint inhibitor drugs that train the immune system to identify and destroy cancer cells. Using the drug factory beads on their own mouse models of mesothelioma saw more than 50% of the tumors destroyed. Combining them with a checkpoint inhibitor drug completely destroyed all tumors in seven mice that were treated, in just a few days.

“It’s very hard to treat mesothelioma tumors in mice, like it is in human beings,” said Burt. “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.”

Based on their previous results, the team has received approval for clinical trials in ovarian cancer patients beginning this US fall. The results of this latest round of experiments mean that another clinical trial focusing on mesothelioma patients mightn’t be too far behind.

“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,” said study author Omid Veiseh. “We have held meetings with the FDA and expect to initiate a second trial for this patient population in the latter half of 2023.”

The research was published in the journal Clinical Cancer Research.

Source: Rice University

Earlier this year, scientists at Rice University demonstrated a highly promising approach to tackling ovarian and colorectal cancer that centered on “drug factory” beads that could be implanted alongside tumors to destroy them in less than a week. By combining this technology with other immunotherapy drugs, the scientists have now explored the potential for this technique to tackle another form of cancer, and achieved very similar results.

The drug factory beads developed by the Rice University team are around the size of a pinhead and are loaded up with tens of thousands of cells genetically engineered to produce interleukin-2 (IL-2). This cytokine naturally activates white blood cells to fight cancer and is approved by the FDA as an immunotherapy treatment for cancer.

By implanting the beads alongside tumors in mouse models of ovarian and colorectal cancer, the drug factories were so effective at continually generating IL-2 that the growths were eradicated in as little as six days. These exciting results caught the eye of another group of researchers working on treatments for mesothelioma, a type of cancer that forms in the tissue lining around internal organs. Around 80 percent of mesothelioma cases are tied to prolonged asbestos exposure.

“I take care of patients who have malignant pleural mesothelioma,” said Dr. Bryan Burt, from Baylor College of Medicine. “This is a very aggressive malignancy of the lining of the lungs. And it’s 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.”

Burt and his colleagues sought to combine the drug factory technology with another form of immunotherapy that has shown some promise in treating mesothelioma, in the form of checkpoint inhibitor drugs that train the immune system to identify and destroy cancer cells. Using the drug factory beads on their own mouse models of mesothelioma saw more than 50% of the tumors destroyed. Combining them with a checkpoint inhibitor drug completely destroyed all tumors in seven mice that were treated, in just a few days.

“It’s very hard to treat mesothelioma tumors in mice, like it is in human beings,” said Burt. “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.”

Based on their previous results, the team has received approval for clinical trials in ovarian cancer patients beginning this US fall. The results of this latest round of experiments mean that another clinical trial focusing on mesothelioma patients mightn’t be too far behind.

“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,” said study author Omid Veiseh. “We have held meetings with the FDA and expect to initiate a second trial for this patient population in the latter half of 2023.”

The research was published in the journal Clinical Cancer Research.

Source: Rice University