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Tiny ‘drug factories’ kill cancer in mice in days

Nash and Veiseh with vials of bead-like "drug factories" they created to treat cancer. The beads are designed to continuously produce natural compounds that program the immune system to attack tumors. (Credit: Jeff Fitlow/Rice)

A new immunotherapy treatment can eradicate advanced-stage ovarian and colorectal cancer in mice in as little as six days, researchers report.

The therapy could be ready for human clinical trials later this year.

Researchers used implantable “drug factories” the size of a pinhead to deliver continuous, high doses of interleukin-2, a natural compound that activates white blood cells to fight cancer.

“We just administer once, but the drug factories keep making the dose every day, where it’s needed until the cancer is eliminated.”

The drug-producing beads can be implanted with minimally invasive surgery. Each contains cells engineered to produce interleukin-2 that are encased in a protective shell.

Human clinical trials could begin as soon as this fall because one of the key design criteria was helping cancer patients as quickly as possible, says Omid Veiseh, an assistant professor of bioengineering at Rice University, whose lab produced the treatment.

The researchers chose only components that had previously proven safe for use in humans, and they have rated the safety of the new treatment in multiple tests.

“We just administer once, but the drug factories keep making the dose every day, where it’s needed until the cancer is eliminated,” Veiseh says.

“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.”

As reported in Science Advances, the researchers placed drug-producing beads beside tumors and within the peritoneum, a sac-like lining that supports intestines, 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 anti-tumor immunity while avoiding systemic side effects of cytokines and other pro-inflammatory drugs,” says coauthor Amir Jazaeri, professor of gynecologic oncology and reproductive medicine at MD Anderson.

“In this study, we demonstrated that the ‘drug factories’ allow regulatable local administration of interleukin-2 and eradication of tumor in several mouse models, which is very exciting. This provides a strong rationale for clinical testing.”

Interleukin-2 is a cytokine, a protein the immune system uses to recognize and fight disease. It is an FDA-approved cancer treatment, but lead author Amanda Nash, a graduate student in Veiseh’s group, says 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 says. “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 same general approach used in the study could be applied to treat cancers of the pancreas, liver, lungs, and other organs, Nash says. The drug factories could be placed next to tumors and within the linings that surround those organs and most others, she says.

And 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.

The bead’s outer shell shields its cytokine-producing cells from immune attacks. The shells are made of materials the immune system recognizes as foreign objects but not as immediate threats, and Veiseh’s lab leveraged that in its design.

“We found foreign body reactions safely and robustly turned off the flow of cytokine from the capsules within 30 days,” he says. “We also showed we could safely administer a second course of treatment should it become necessary in the clinic.”

Additional coauthors are from the University of Houston, the University of Virginia, the University of Texas MD Anderson Cancer Center, CellTrans Inc., and Rice.

The Cancer Prevention Research Institute of Texas, Avenge Bio, the Emerson Collective, the Welch Foundation, the Rice University Academy of Fellows, the National Science Foundation, and the National Institutes of Health funded the work.

Avenge Bio, a Massachusetts-based startup cofounded by Veiseh, has licensed the cytokine-factory technology from Rice. Jazaeri receives compensation as a consultant on Avenge Bio’s scientific advisory board and has disclosed the relationship to MD Anderson in accordance with its conflict-of-interest policy. Nash, Veiseh, and coauthors Maria Jarvis, Samira Aghlara-Fotovat, Sudip Mukherjee, Andrew Hecht, Oleg Igoshin, and David Zhang declared interests via patents filed by Rice on the cytokine factories. Igoshin, Veiseh, and José Oberholzer are paid consultants for Avenge Bio. Nash, Zhang, Rahul Sheth, Oberholzer, Jazaeri, and Veiseh hold equity in Avenge Bio.

Source: Rice University