Bioengineers at Rice University have demonstrated that they can eradicate advanced ovarian and colorectal cancer in mice within just six days—and the treatment could potentially enter human clinical trials later this year. The researchers used a needle-sized implantable "drug factory" delivering sustained high doses of interleukin-2 (IL-2), a natural compound that activates white blood cells to fight cancer.

The drug-producing beads, which can be implanted through minimally invasive surgery, contain cells enclosed in a protective shell that are engineered to produce IL-2. The study was conducted by Dr. Omid Veiseh, Amanda Nash, and colleagues from Rice University, MD Anderson Cancer Center, the University of Virginia, and other institutions.

Dr. Veiseh, Assistant Professor of Bioengineering whose lab developed the treatment, said human clinical trials could begin as early as this fall—because one of his team's key design criteria was to help cancer patients as quickly as possible. The group selected only components previously proven safe for human use and demonstrated the new therapy's safety in multiple tests.

"We administer just once, but the drug factory produces the dose every day until the cancer is eliminated," Veiseh said. "Once we determined the right dose—how many factories we need—we were able to eradicate 100% of animals with ovarian cancer and 7 out of 8 with colorectal cancer."

In the newly published study, researchers placed the drug-producing beads next to tumors and within the peritoneum—the sac-like lining that supports the intestines, ovaries, and other abdominal organs. Placing IL-2 in this cavity concentrates it within the tumor while limiting exposure elsewhere.

Dr. Amir Jazaeri, Professor of Gynecologic Oncology and Reproductive Medicine at MD Anderson and study co-author, stated: "A major challenge in the immunotherapy field is increasing tumor inflammation and anti-tumor immunity while avoiding systemic side effects of cytokines and other pro-inflammatory drugs. In this study, we demonstrated that the 'drug factory' allows regulated local delivery of IL-2 and tumor eradication in several mouse models—very exciting and providing a strong rationale for clinical testing."

IL-2 is a cytokine—a protein the immune system uses to identify and fight disease. It is an FDA-approved cancer treatment, but Nash—a graduate student in Veiseh's lab and first author—said the drug factories elicit stronger immune responses than existing IL-2 regimens because the beads deliver higher concentrations directly to the tumor.

"If you delivered the same concentration via IV pump, it would be highly toxic," Nash said. "With the drug factory, concentrations elsewhere in the body are actually lower than what patients tolerate from IV therapy. High concentrations are only at the tumor site."

The same general approach could be applied to treat pancreatic, liver, lung, and other cancers. Drug factories can be placed near tumors and the linings surrounding these organs. If different cytokines are needed to target specific cancer types, the beads can be loaded with engineered cells producing the appropriate immunotherapeutic compounds. The bead shells protect cytokine-producing cells from immune attack.

Veiseh's lab leveraged the foreign body response in design: "We found that the foreign body response safely and robustly shuts off cytokine flow from the capsules within 30 days. We also showed that if clinically necessary, we can safely administer a second course of treatment."