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Bioengineers at Rice University in Texas (USA) have shown that they can eliminate ovarian and colorectal cancer at an advanced stage in mice in as little as six days with an implantable treatment of drug-producing pearls, which might be ready for human clinical trials later this year.
The researchers used pinhead-sized implantable “drug factories” to deliver continuous high doses of interleukin-2a natural compound that activates white blood cells to fight cancer.
Each of the drug-producing beads contains cells designed to produce interleukin-2 that are encased in a protective shell and can be implanted with minimally invasive surgery. The treatment and the results of the animal tests are published this Wednesday in the journal “Science Advances”.
Omid Veiseh, an assistant professor of bioengineering whose lab produced the treatment, says that human clinical trials might start this fall because one of his team’s key design criteria was to help cancer patients as quickly as possible. To do this, they chose only components that had previously been shown to be safe for use in humans, and the safety of the new treatment has been proven in multiple tests.
«We only manage once, but the drug factories continue to produce the dose every day, in the place where it is needed until the cancer is eliminated, “explains Veiseh. “Once we determined the correct dose (how many factories we needed) we were able to eradicate tumors in 100% of the animals with ovarian cancer and in seven of the eight animals with colorectal cancer.”
In the recently published study, the researchers placed drug-producing beads next to tumors and within the peritoneum, ovaries, and other abdominal organs. Placement within this cavity concentrated interleukin-2 within tumors and limited exposure elsewhere.
“A major challenge in the field of immunotherapy is to increase tumor inflammation and antitumor immunity while avoiding systemic side effects of cytokines and other proinflammatory drugs,” says study co-author Dr. Amir Jazaeri, Professor of gynecologic oncology and reproductive medicine at MD Anderson. ‘In this study we show that ‘drug factories’ enable locally regulatable interleukin-2 delivery and tumor eradication in various mouse models, which is very exciting. This provides a strong rationale for clinical trials,” he adds.
Interleukin-2 is a cytokine, a protein that the immune system uses to recognize and fight disease. It’s an FDA-approved cancer treatment, but Amanda Nash, a graduate student in Veiseh’s group and the study’s lead author, says the drugmakers elicit a stronger immune response than interleukin-2 treatment regimens. existing because pearls managehigher concentrations of the protein directly to tumors.
“If you were to give the same concentration of protein through an IV pump it would be extremely toxic,” says Nash. “With drug factories, the concentration that we see in other parts of the body, far from the tumor site, is actually lower than what patients have to tolerate with intravenous treatments. The high concentration is only at the tumor site», he defends.
In Nash’s opinion, the same general approach used in the study might be applied to treating cancers of the pancreas, liver, lungs and other organs. Drug factories might be placed next to tumors and within the linings surrounding those organs and most others. And if a different cytokine is needed to attack a specific form of cancer, pearls can be loaded with modified cells that produce that immunotherapeutic compound.
The outer shell of the pearl protects the cytokine-producing cells from immune attack. The shells are made of materials that the immune system recognizes as foreign objects but not as immediate threats, and Veiseh’s lab took advantage of that in its design.
“We found that foreign body reactions safely and robustly shut down the flow of cytokines from the capsules within 30 days. We also showed that we might safely administer a second course of treatment should it become necessary in the clinic,” says Veiseh.
