A new treatment that combines “drug factory” cytokine implants with a checkpoint inhibitor drug eradicates advanced mesothelioma tumors in mice in just days, a new study shows.
Researchers injected drug-producing beads no larger than the size of a pinhead near tumors, where they could continuously produce high doses of interleukin-2 (IL-2), a natural compound that activates white blood cells to fight cancer.
“From the beginning, our goal was to develop a platform therapy that could be used for several different types of immune system disorders or different types of cancer,” says Amanda Nash, a graduate student at Rice University who has been developing the implant technology for several years. with one of the study’s lead authors, Samira Aglaro-Fotovat, a fellow student in the lab of bioengineer Amid Weisekh.
The cytokines factories consist of alginate beads loaded with tens of thousands of cells that have been genetically engineered to produce natural IL-2, one of two cytokines approved by the FDA to treat cancer.
“…I have not seen these mesothelioma tumors in mice being killed as efficiently as in this mouse model.”
The factories are only 1.5 millimeters wide and can be implanted using minimally invasive surgery to deliver high doses of IL-2 directly to tumors. In the mesothelioma study, researchers placed the beads near tumors and inside a thin layer of tissue known as the pleura, which covers the lungs and lines the inner chest wall.
“I care for patients with malignant pleural mesothelioma,” says Brian Burt, professor and chief of thoracic surgery at Baylor University. “This is a very aggressive malignant tumor of the lining of the lungs. And it is very difficult to completely treat surgically.
“In other words, residual disease often remains. Treating this residual disease with local immunotherapy — the local delivery of relatively high doses of immunotherapy into the pleural space — is a very attractive way to treat this disease.”
Weissech says the mesothelioma research began when Burt and Ravi Ganta, an associate professor at Baylor, heard about the first results ovarian cancer Veiseh’s team conducted animal tests with collaborators from the University of Texas MD Anderson Cancer Center.
In March, colleagues at Veiseh and MD Anderson published a study showing that IL-2-producing beads could eliminate late-stage ovarian and rectal tumors in mice in less than a week.
“They were very impressed with our preclinical data on ovarian cancer,” Weisse says of Burt and Ganta. “And they asked the question, ‘Can we actually use the same system to treat mesothelioma?’
Mesothelioma is any cancer that occurs in the tissues that surround and protect internal organs. About 80% of mesothelioma cases are related to prolonged exposure asbestos.
Immunotherapy with drugs called checkpoint inhibitors has had some success in treating mesothelioma. Checkpoint inhibitors do not kill cancer directly, but rather by teaching the immune system to recognize and destroy cancer cells.
In the mesothelioma study, researchers tested Veiseh’s drug-producing implants either alone or in combination with a checkpoint inhibitor that targets the PD-1 protein. They found that the drug factory implants eliminated tumors in more than 50% of the animals used alone.
Tumors were completely destroyed in all seven mice that received the drug factory implants and the PD-1 checkpoint inhibitor.
“It’s very difficult to treat mesothelioma tumors in mice, just like in humans,” Burt says. “Our data show that regional delivery of these immunotherapy particles to mice with mesothelioma has highly provocative and highly effective treatment responses. In fact, I have not seen these mesothelioma tumors in mice killed as efficiently as in this mouse model.”
The results also show that a combination of IL-2-producing implants and anti-PD-1 checkpoint inhibitors may be effective in training “memory T cells” that can reactivate the immune system to fight mesothelioma when it recurs, Weisse says. .
“We have a spin-off company called Avenge Bio that recently received FDA approval to treat patients with ovarian cancer, and they plan to start treating these IL-2 cytokine factories in the next few months,” Weisse says.
“The preclinical data presented in our latest manuscript helped justify the initiation of a second clinical trial for patients suffering from mesothelioma and other types of lung cancer with pleural metastases,” says Weisse. “We have held meetings with the FDA and expect to start a second trial for this group of patients in the second half of 2023.”
In addition to their cancer research, Weise and Gant received a grant from the American Heart Association to study the potential of cytokine implants to treat heart damage caused by heart attacks.
The study was published in Clinical research on cancer. The Cancer Prevention and Research Institute of Texas, the National Science Foundation and the National Institutes of Health funded the work.
Source: Rice University