University of Illinois Chicago scientists have redesigned a treatment for the most common pediatric leukemia to eliminate its severe side effects, like blood clots and liver damage. If approved, the new drug may be tolerated by a broader range of leukemia patients and even be used to treat other cancers.
The team led by UIC’s Arnon Lavie created a new form of asparaginase, an enzyme approved clinically for acute lymphoblastic leukemia, the most common blood cancer in children. Using protein engineering, the team designed a new biologic compound that tries to maximize the therapeutic effects of the enzyme while reducing toxicity and harmful responses in the patient.
In a paper in Cancer Letters, Lavie and co-authors from UIC and Ghent University in Belgium reported that their compound successfully destroyed leukemia cells in mice without the common side effects of asparaginase. The new treatment also shrank tumors in laboratory models of additional cancers, such as melanoma and liver cancer.
These encouraging results boost the ongoing efforts of Lavie’s research group to bring their novel enzyme to clinical trials. In 2023, the National Cancer Institute Experimental Therapeutics Program chose his company, Enzyme by Design, to perform the preclinical work needed for approval to test the drug in humans.
“I am excited for the opportunity to translate my academic research into a potential treatment that addresses an unmet need,” said Lavie, UIC professor of biochemistry and molecular genetics and a member of the University of Illinois Cancer Center. “The reality is that the pharmaceutical industry is primarily interested in de-risked molecules, and our goal is to de-risk our novel asparaginase sufficiently so that it becomes an interesting therapeutic for a company.”
The research team is already on track to pursuing clinical trials. After establishing Enzyme by Design with support from the UIC Office of Technology Management, the project has received nearly $4 million in funding, according to Amanda Schalk, research assistant professor at UIC who has been involved in the project since it started in 2011.
“It has been incredible to see the progress made from discovery to drug development over the past 13 years,” Schalk said. “It’s so exciting the further along we get on the path to the clinic to provide life-changing benefits to patients.”
Through that support, the group is conducting the toxicity, pharmacokinetic and manufacturing studies necessary for permission from the FDA to begin their first clinical trials.
Additional UIC co-authors on the paper included Ying Su, Ashley De Loera, Alyssa Garcia and Hui Chen. The research was funded in part by grants from the National Institutes of Health and the U.S. Department of Veteran Affairs.
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