Rice University researchers have successfully eradicated advanced-stage ovarian and colorectal cancer in mice in as little as six days by implementing a potentially breakthrough cancer treatment that uses polymer-coated human cells to deliver anti-tumor compounds, according to a report from Rice University.
The implantable bead-like devices that researchers called “drug factories” deliver cytokines to treat animal tumors, and it would appear the treatment could also be used in humans, researchers reported in last week in Science Advances.
Cytokines, as the study explains, “are soluble molecular messengers that activate and propagate disease-fighting immune cascades in the body in response to stimuli from antigen-presenting cells.”
The clinically translatable cytokine delivery platform Rice researchers developed is “composed of polymer-encapsulated human ARPE-19 (RPE) cells that produce natural cytokines” such as Interleukin-2, a compound approved by the Food and Drug Administration (FDA) for treatment of renal cancer and melanoma, the Science Advances report said.
Dr Amir Jazaeri, a gynecology professor at Rice and co-author of the study, explained in the Rice University publication that high doses of cytokines in the blood stream can prove to be toxic and dangerous. Therefore, he said, “the major challenge in the field of immunotherapy is to increase tumor inflammation and anti-tumor immunity while avoiding systemic side effects of cytokines.”
To get around this issue, the researchers developed the pinhead-sized “drug factory,” which can be implanted with minimally invasive surgery either on or near the cancerous tumor and within the linings that surround those organs.
The drug factory continuously delivers high doses of interleukin-2, directing the immune system to address the tumor, researchers said. Some patients only need one factory while some require multiple factories to generate the necessary dosage, they added.
The implant is designed to have a protective coating that prevents its destruction by the immune system before it arrives at its intended destination.
“Once we determined the correct dose—how many factories we needed—we were able to eradicate tumors in 100% of animals with ovarian cancer and in seven of eight animals with colorectal cancer,” said Dr. Omid Veiseh, an assistant professor of bioengineering at Rice and a co-author of the study.
“We found foreign body reactions safely and robustly turned off the flow of cytokine from the capsules within 30 days,” he said. “We also showed we could safely administer the second course of treatment should it become necessary in the clinic.”
Dosage well delivered
Dr. Amanda Nash, a graduate student in Veiseh’s group and the study’s lead author, explained that “the drug factories provoke a stronger immune response than existing interleukin-2 treatment regimens because the beads deliver higher concentrations of the protein directly to tumors.”
“If you gave the same concentration of the protein through an IV pump, it would be extremely toxic,” Nash said. “With the drug factories, the concentration we see elsewhere in the body, away from the tumor site, is actually lower than what patients have to tolerate with IV treatments. The high concentration is only at the tumor site.”
If a different cytokine is needed to target a specific form of cancer, the beads can be loaded with engineered cells that make that immunotherapeutic compound, Nash said. She said she believes the devices could also be altered for use, among others, against the pancreas, liver, and lung cancer.
According to the American Cancer Society, colorectal cancer is diagnosed in around 150,000 Americans every year and is the third leading cause of death among men and women in the US, while ovarian cancer affects nearly 20,000 women every year, killing around 12,000.
Veiseh said human clinical trials for this device could start as early as this fall.