Describing the new technique in the journal Science Advances, researchers explain how they inserted tiny “drug factories” into the lining around the animals’ organs, resulting in the destruction of tumors in just six days.
These implants contain engineered human cells programmed to secrete interleukin-2 (IL-2), a cytokine that activates white blood cells to fight cancer and other diseases.
The use of IL-2 and other cytokines for the treatment of skin and kidney cancers has already been approved by the US Food and Drug Administration (FDA), yet existing therapies involve the intravenous (IV) injection of high doses of these compounds, often resulting in negative side-effects.
The researchers sought to develop a new delivery system supplying high doses of IL-2 only to the cancer site itself without producing major systemic increases in cytokine levels. To achieve this, they implanted their drug factories into the peritoneum – a sac-like lining supporting the intestines, ovaries, and other abdominal organs – thus ensuring IL-2 delivery directly to the adjacent tumors.
“We just administer once, but the drug factories keep making the dose every day, where it’s needed until the cancer is eliminated,” explained study author Omid Veiseh in a statement. “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.”
The fact that the factories could pump IL-2 directly to the tumors from the peritoneum resulted in a more targeted immune response than is typically seen with existing cytokine-based treatments. Importantly, the researchers detected no major systemic increases in IL-2 levels, implying that this delivery method may eliminate many of the side effects associated with current therapies.
“If you gave the same concentration of the protein through an IV pump, it would be extremely toxic,” said study author Amanda Nash. “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.”
The drug factories consist of interleukin-producing cells encased in a protective shell that prevents the body’s immune system from recognizing them as an immediate threat. This allows these cells to remain within a patient’s body and function for 30 days before finally being destroyed by the immune system.
Because IL-2 and other cytokines are already approved for medical use, the researchers say this minimally-invasive technique could progress through the clinical trial process extremely rapidly, with human trials starting later this year. They also explain that the method could be adapted for multiple different cancer types by placing the drug factories into the lining surrounding any organ harboring a tumor.
Summing up their findings, the researchers state that “this technology provides the field with an invaluable tool that can be easily modified and leveraged for other peritoneal cancers including renal, liver, pancreatic, and cervical cancers in future clinical studies.”