Could ‘drug factory’ beads help combat cancer?

Implantable ‘drug factories’ have been shown to eradicate advanced-stage ovarian and colorectal cancer in mice in as little as six days. According to Rice University bioengineers, the treatment could be ready to enter human clinical trials later this year.

The researchers used implantable drug factories the size of a pinhead to deliver continuous, high doses of interleukin 2 (IL-2), a natural activator of white blood cells and US Food and Drug Administration (FDA)-approved cancer treatment. The drug-producing beads can be implanted with minimally invasive surgery. Each bead contains cells engineered to produce IL-2 encased in a protective shell.

The treatment and animal test results are described in a paper published in Science Advances, co-authored by Omid Veiseh, Amanda Nash and colleagues from Rice, the University of Texas MD Anderson Cancer Center, the University of Virginia and others.

Veiseh, an assistant professor of bioengineering whose lab produced the treatment, said human clinical trials could begin as soon as this Autumn, since part of the team’s design criteria was helping cancer patients as quickly as possible and thus they chose only components that had previously proven safe for use in humans. Additionally, the safety of the of the new treatment has been evaluated in multiple tests.

“We just administer once, but the drug factories keep making the dose every day, where it is needed until the cancer is eliminated,” Veiseh explained. “Once we determined the correct dose — how many factories we needed — we were able to eradicate tumours in 100 percent of animals with ovarian cancer and in seven of eight animals with colorectal cancer.”

Rice University bioengineer Omid Veiseh with a vial of bead-like implants his lab invented to serve as anti-cancer drug factories. Veiseh and colleagues showed the implants could eradicate ovarian and colorectal cancer in mice in as little as six days [Credit: Photo by Jeff Fitlow/Rice University].

In the study, researchers placed drug-producing beads beside tumours and within the peritoneum, a sac-like lining that supports intestines, ovaries and other abdominal organs. Placement within this cavity concentrated IL-2 within tumours and limited exposure elsewhere.

“A major challenge in the field of immunotherapy is to increase tumour inflammation and anti-tumour immunity while avoiding systemic side effects of cytokines and other pro-inflammatory drugs,” noted study co-author Dr 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 tumour in several mouse models, which is very exciting. This provides a strong rationale for clinical testing.”

Though IL-2 is an FDA-approved cancer treatment, Nash, a graduate student in Veiseh’s group and the study’s lead author, revealed that the drug factories provoke a stronger immune response than existing IL-2 treatment regimens because the beads deliver higher concentrations of the protein directly to tumours. “If you gave the same concentration of the protein through an IV [(intravenous)] pump, it would be extremely toxic,” Nash stated. “With the drug factories, the concentration we see elsewhere in the body, away from the tumour site, is actually lower than what patients have to tolerate with IV treatments. The high concentration is only at the tumour site.”

Nash said the same general approach used in the study could be applied to treat cancers of the pancreas, liver, lungs and other organs, by placing the drug factories next to the tumours and within the linings that surround those organs and most others. Additionally, 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 protects the cytokine-producing cells from immune attacks. The shells are made of materials the immune system recognises 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 stated. “We also showed we could safely administer a second course of treatment should it become necessary in the clinic.”

Avenge Bio, a Massachusetts-based startup co-founded by Veiseh, has licensed the cytokine-factory technology from Rice.

The research was funded by the Cancer Prevention Research Institute of Texas (RR160047), Avenge Bio, the Emerson Collective, the Welch Foundation, the Rice University Academy of Fellows, the National Science Foundation (1842494) and the National Institutes of Health (R01DK120459).