Researchers have reported a new version of asparaginase, tested in mice, which may improve treatment for acute lymphoblastic leukaemia.
The researchers in Chicago, USA, have engineered a new version of the asparaginase enzyme, with the aim of eliminating the severe side effects linked to the treatment, such as blood clotting and liver damage.
So far, the treatment has been tested on laboratory mice. Reporting in Cancer Letters, the researchers say that it successfully destroyed leukaemia with fewer side-effects; compared with mice treated with traditional asparaginase, there was no loss of body weight.
The treatment is based on an asparaginase enzyme derived from guinea pigs. The researchers are now taking the steps necessary to begin clinical trials.
Researcher Professor Arnon Lavie, of the University of Illinois, Chicago, USA, said: “The molecular structures told us where we can make changes that would not interfere with the structure, stability or activity of the enzyme. Then we leveraged the fact that the body is tolerant to human-like proteins, which would allow kids and other patients to successfully complete their cancer treatment.”
After ‘humanising’ the protein, the researchers found that their changes also extended its half-life. Prof Lacie said the extended half-life “was a very happy accident, which turns out to be extremely important. Ultimately, it means that you can treat the patient with a lower dose, and with a longer interval between treatments.”
Fellow researcher Dr Amanda Schalk said: “It has been incredible to see the progress made from discovery to drug development over the past 13 years. It’s so exciting the further along we get on the path to the clinic to provide life-changing benefits to patients.”
Source:
Van Trimpont M, Schalk AM, Hofkens K, Peeters E, T'Sas S, Vandemeulebroecke K, Su Y, De Loera A, Garcia A, Chen H, Lammens T, Van Vlierberghe P, Goossens S, Lavie A. (2025) “A human-like glutaminase-free asparaginase is highly efficacious in ASNSlow leukemia and solid cancer mouse xenograft models.” Cancer Letters, 28 February 2025, doi: 10.1016/j.canlet.2024.217404.
Link: https://www.sciencedirect.com/science/article/pii/S0304383524007997
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