Immunotherapy treatment could begin human clinical trials this year

Rice University bioengineers have shown they can eradicate advanced-stage ovarian and colorectal cancer in mice in as little as six days with a treatment that could be ready for human clinical trials later this year.

The researchers used pinhead-sized implantable “drug factories” to continuously deliver high doses of interleukin-2, a natural compound that activates white blood cells to fight cancer. The drug-producing beads can be implanted by minimally invasive surgery. Each contains cells designed to produce interleukin-2 which are encased in a protective shell.

The results of the treatment and animal testing are described online today in a Scientists progress study co-authored by Omid Veiseh, Amanda Nash and colleagues from Rice, University of Texas MD Anderson Cancer Center, University of Virginia and others.

Veiseh, an assistant professor of bioengineering whose lab produced the treatment, said human clinical trials could begin as early as this fall because one of his team’s main design criteria was to help patients with cancer as soon as possible. The team only chose compounds that had previously been shown to be safe for use in humans, and they demonstrated the safety of the new treatment in multiple tests.

“We only administer once, but the pharmaceutical factories continue to manufacture the dose every day where it is needed until the cancer is eliminated,” Veiseh said. “Once we figured out the right dose – how many plants we needed – we were able to eradicate tumors in 100% of the animals with ovarian cancer and in seven out of eight animals with one. colorectal cancer.”

In the recently published study, researchers placed drug-producing beads next to tumors and into the peritoneum, a sac-like lining that supports the intestines, ovaries and other abdominal organs. Placement in this cavity concentrated interleukin-2 in the tumors and limited exposure elsewhere.

“A major challenge in the field of immunotherapy is to increase tumor inflammation and anti-tumor immunity while avoiding the systemic side effects of cytokines and other pro-inflammatory drugs,” said the co- author of the study, Dr. Amir Jazaeri, professor of gynecological and reproductive oncology. medicine at MD Anderson. “In this study, we have demonstrated that ‘drug factories’ enable regulated local delivery of interleukin-2 and tumor eradication in multiple mouse models, which is very exciting. This provides strong justification for clinical trials.”

Interleukin-2 is a cytokine, a protein used by the immune system to recognize and fight disease. It’s an FDA-approved cancer treatment, but Nash, a graduate student in Veiseh’s group and the study’s lead author, said drug factories elicit a stronger immune response than drug regimens. to interleukin-2, as the beads directly deliver higher concentrations of the protein. to tumours.

“If you gave the same concentration of protein via an IV pump, it would be extremely toxic,” Nash said. “With 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 elevated concentration is only at the site of the tumor. tumor.”

Nash said the same general approach used in the study could be applied to treat cancers of the pancreas, liver, lungs and other organs. Drug factories could be placed next to tumors and in the linings that surround these and most other organs, she said. 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 pearl’s outer shell protects its cytokine-producing cells from immune attack. The shells are made of materials that the immune system recognizes as foreign objects but not immediate threats, and Veiseh’s lab took advantage of this in its design.

“We found safe and robust foreign body reactions that turned off the flow of cytokines from the capsules within 30 days,” he said. “We also showed that we could safely administer a second treatment if it became necessary at the clinic.”

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

Additional co-authors include Maria Jarvis, Samira Aghlara-Fotovat, Sudip Mukherjee, Andrea Hernandez, Andrew Hecht, Yufei Cui, Shirin Nouraein, Jared Lee, David Zhang, and Rice’s Oleg Igoshin; Peter Rios, Sofia Ghani, Ira Joshi and Douglas Isa of CellTrans Inc.; Chunyu Xu and Weiyi Peng from the University of Houston; Rahul Sheth of MD Anderson; and José Oberholzer of CellTrans Inc. and the University of Virginia.

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 ) .

Jazaeri receives compensation as a consultant on Avenge Bio’s Scientific Advisory Board and has disclosed the relationship with MD Anderson in accordance with its conflict of interest policy. Nash, Jarvis, Aghlara-Fotovat, Mukherjee, Hecht, Igoshin, Zhang and Veiseh expressed interest via patents filed by Rice on cytokine factories. Igoshin, Veiseh and Oberholzer are paid consultants for Avenge Bio. Nash, Zhang, Sheth, Oberholzer, Jazaeri and Veiseh hold a stake in Avenge Bio.


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