Mesothelioma cure? Tiny ‘drug factory’ implants successfully destroy lung cancer tumors


HOUSTON — Tiny beads packed with cancer-killing cells may finally provide a cure for mesothelioma — one of the most aggressive forms of lung cancer. Moreover, researchers from Rice University and the Baylor College of Medicine say they can implant this cytokine “drug factory” into patients through a minimally invasive surgery.

In the new study, the team reports that combining the drug-producing beads with a standard checkpoint inhibitor drug completely destroyed mesothelioma tumors in a group of lab mice. Even without the checkpoint inhibitor, the new drug factory was able to eradicate tumors in over half of the animals on its own.

Packing a drug factory into the head of a pin

This new approach to cancer treatment uses drug-producing beads, which are smaller than the head of a pin. After doctors implant them next to a cancerous tumor, the beads continuously produce high doses of interleukin-2 (IL-2), a natural substance that activates white blood cells to fight cancer.

The drug factory’s success in fighting mesothelioma is the latest victory using this cancer-killing platform, invented by the lab of Rice bioengineer Omid Veiseh. The U.S. Food and Drug Administration (FDA) have given its approval to begin clinical trials of the technology in ovarian cancer patients starting this fall.

“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,” says Rice graduate student Amanda Nash in a university release.

The tiny cytokine factories consist of alginate beads which scientists load with tens of thousands of cells genetically engineered to produce IL-2. This particular substance is one of two FDA-approved cytokines for cancer treatment.

These “factories” are just 1.5 millimeters wide and are small enough for doctors to implant right next to a tumor through a minimally invasive operation. For treating mesothelioma, the team placed the beads inside a thin layer of tissue called the pleura. The tissue covers the lungs and lines the interior chest wall.

What is mesothelioma?

Mesothelioma includes any cancer that forms in the tissue linings which surround the internal organs. However, its strongly associated with lung cancer and roughly 80 percent of all mesothelioma cases have a connection to prolonged exposure to asbestos.

“I take care of patients who have malignant pleural mesothelioma,” says Dr. Bryan Burt, professor and chief of Baylor’s Division of Thoracic Surgery in the Michael E. DeBakey Department of Surgery. “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.”

The mesothelioma study began after Dr. Burt and Baylor associate professor Dr. Ravi Ghanta heard about Veiseh’s success with ovarian cancer animal tests. Those experiments found that IL-2-producing beads could destroy advanced-stage ovarian and colorectal tumors in less than a week.

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

The drug factory still needs help from other treatments

Immunotherapy with drugs called checkpoint inhibitors have had some success in treating mesothelioma. However, they don’t kill cancer directly. Checkpoint inhibitors train the immune system to recognize and destroy cancer cells.

During the new study, researchers found that implanting the drug factories on their own destroyed over 50 percent of the mesothelioma tumors in a group of lab mice. When the team paired the treatment with a checkpoint inhibitor that targets the PD-1 protein, the combination destroyed all of the tumors in a group of seven mice.

“It’s very hard to treat mesothelioma tumors in mice, like it is in human beings,” Burt explains. “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 notes that pairing the bead implants with an anti-PD-1 checkpoint inhibitor may also help the body’s “memory T cells” learn to fight mesothelioma if the disease ever returns.

“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,” Veiseh concludes.

“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. 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 study is published in the journal Clinical Cancer Research.

Comments

  1. Produces cytokine to help combat cancer cells.

    Just give them COVID -the cytokine storms should wipe out the cancer toot sweet.

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