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In mice, ‘drug factory’ implants prevent ovarian and colorectal cancer

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Bioengineers have shown that a therapy that might be ready for human clinical trials later this year can destroy advanced-stage ovarian and colorectal cancer in mice in as little as six days.

Rice University bioengineers have shown that a therapy that might be ready for human clinical trials later this year can destroy advanced-stage ovarian and colorectal cancer in mice in as little as six days.

The researchers employed pinhead-sized implanted “drug factories” to provide large dosages of interleukin-2, a natural molecule that stimulates white blood cells to attack cancer, on a continual basis. Minimally invasive surgery may be used to implant the drug-producing beads. Each one is made up of cells that have been genetically modified to manufacture interleukin-2 and are enclosed in a protective shell.

Omid Veiseh, Amanda Nash, and colleagues from Rice, the University of Texas MD Anderson Cancer Center, the University of Virginia, and others detail the therapy and animal test findings in a Science Advances report published today.

Human clinical trials might begin as soon as this autumn, according to Veiseh, an assistant professor of bioengineering whose group developed the therapy. One of his team’s primary design requirements was to help cancer patients as swiftly as feasible. Only components that have previously been shown safe for use in humans were chosen, and the new treatment’s safety has been demonstrated in many studies.

“We just give it once, but the drug factories keep producing the dosage every day until the cancer is gone,” Veiseh said. “Once we figured out the right dosage — how many factories we needed — we were able to eliminate tumors in 100 percent of ovarian cancer patients and seven out of eight colorectal cancer patients.”

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Researchers inserted drug-producing beads alongside tumors and inside the peritoneum, a sac-like lining that supports the intestines, ovaries, and other abdominal organs, in a recently published study. The placement of interleukin-2 into this hollow focused it within tumors while limiting exposure elsewhere.

“Increasing tumor inflammation and anti-tumor immunity while avoiding systemic side effects of cytokines and other pro-inflammatory drugs is a major challenge in the field of immunotherapy,” said study co-author Dr. Amir Jazaeri, professor of gynecologic oncology and reproductive medicine at MD Anderson. “We showed in this work that the ‘drug factories’ enable for controlled local delivery of interleukin-2 and tumor elimination in numerous mouse models, which is quite intriguing. This establishes a compelling case for clinical testing.”

Interleukin-2 is a cytokine, which is a protein produced by the immune system to identify and fight illness. It’s an FDA-approved cancer treatment, but the drug factories, according to Nash, a graduate student in Veiseh’s lab and the study’s lead author, elicit a stronger immune response than existing interleukin-2 treatment regimens because the beads deliver higher concentrations of the protein directly to tumors.

“It would be exceedingly hazardous if you provided the same dose of protein via an IV pump,” Nash added. “The concentrations we find elsewhere in the body, away from the tumor site, using drug factories are actually lower than what patients must endure with IV therapy. Only at the tumor location is there a large concentration.”

The same basic technique utilized in the research, according to Nash, might be used to treat pancreatic, liver, lungs, and other organ tumors. She believes the drug factories may be positioned near tumors and inside the linings that surround those organs, as well as most others. If a certain kind of cancer requires a distinct cytokine, the beads may be loaded with modified cells that produce that immunotherapeutic chemical.

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The outer shell of the bead protects the cytokine-producing cells from immunological responses. Veiseh’s lab took use of the fact that the shells are constructed of materials that the immune system detects as foreign objects but not as imminent dangers in their design.

“We discovered foreign body responses switched off the flow of cytokine from the capsules safely and robustly within 30 days,” he added. “We also demonstrated that we could safely deliver a second round of therapy in the clinic if it became necessary.”

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

Maria Jarvis, Samira Aghlara-Fotovat, Sudip Mukherjee, Andrea Hernandez, Andrew Hecht, Yufei Cui, Shirin Nouraein, Jared Lee, David Zhang, and Oleg Igoshin of Rice; Peter Rios, Sofia Ghani, Ira Joshi, and Douglas Isa of CellTrans Inc.; Chunyu Xu and Weiyi Peng of University of Houston; Rahul Sheth

The Texas Cancer Prevention Study Institute (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 all contributed to the research (R01DK120459).

Jazaeri is paid as a consultant on Avenge Bio’s scientific advisory board, and the connection has been declared to MD Anderson in compliance with its conflict-of-interest policy. Rice submitted patents on cytokine factories, while Nash, Jarvis, Aghlara-Fotovat, Mukherjee, Hecht, Igoshin, Zhang, and Veiseh reported interests. Avenge Bio pays Igoshin, Veiseh, and Oberholzer as consultants. Avenge Bio is owned by Nash, Zhang, Sheth, Oberholzer, Jazaeri, and Veiseh.

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