2023-06-10 08:23:00
Nanoparticles consisting of a very specific protein first counteract an overreaction of the immune system, but then give that system a boost. This finding opens up possibilities for a therapy against sepsis, a condition in which the immune system is severely disrupted. Immunologists from Radboudumc and bioengineers from Eindhoven University of Technology (TU/e) joined forces and developed and tested an innovative new nanomedicine. Their research results are included Nature Biomedical Engineering.
Sepsis is a life-threatening disease in which the immune system is disrupted by an infection with a bacteria, fungus or virus. This disruption can consist of an excessive immune response, so-called hyperinflammation. As a result, tissues are damaged and organs fail. On the other hand, the immune system can also become exhausted; so much so that it becomes paralyzed. We call this immune paralysis; the body is therefore not very resistant to a new infection.
To combine forces
For years, scientists worldwide have been searching for an effective therapy against sepsis. This entails a search for a drug that simultaneously counteracts both the overreaction and the paralysis of the immune system. The risk here is that a possible remedy for this overreaction will actually lead to paralysis.
Immunologists at Radboudumc discovered in a petri dish with immune cells that the cytokine interleukin-4 counteracts inflammation, while unexpectedly generating trained immunity. This paradoxical property can be used to treat sepsis. Interleukin-4 must target immune cells in the human body. Researchers at Eindhoven University of Technology (TU/e) have extensive experience in developing innovative nanotechnology-based approaches to combat cancer, for example.
Tiny particles
With this approach in mind, TU/e bioengineers designed a new nanotechnology-based approach in which they developed a fusion protein that forms nanoparticles with fat molecules. This type of nanomedicine consists of tiny fat particles made up of endogenous proteins that interact very specifically with immune cells. In this case, bioengineers developed a new protein from interleukin-4 and another body protein that integrates into those fat particles. As a result, interleukin-4 is delivered specifically to immune cells, slowing down the acute inflammatory response, while at the same time boosting the immune system. This balances the immune system.
Mihai Netea, professor of Experimental Internal Medicine at Radboud university medical center: “We know that the protein interleukin-4 counteracts an overreaction of the immune system. We were surprised that this protein in a test tube could also trigger trained immunity in certain immune cells.” Trained immunity is the part of our innate immune system that has a learning capacity and thus strengthens our immune system. To achieve this in humans, TU/e developed this new nanomedicine based on interleukin-4. And it worked, the results indicate. In both blood samples from sepsis patients and laboratory animals, the nanoparticles brought the immune system back on course.
New technology
What is innovative about using this nanotechnology is that the researchers succeeded in directing interleukin-4 to specific immune cells. Willem Mulder, professor of Precision Medicine at both Radboud university medical center and TU/e: “We have been developing new proteins by fusing endogenous proteins for some time now. We also did the same for interleukin-4. We made nanoparticles from it. By injecting these nanoparticles into the bloodstream, interleukin-4 is delivered to the cells where it should end up.”
The researchers emphasize that the therapy has not yet been tested in patients. This requires further research. However, the method is a very innovative form of immunotherapy, which offers new possibilities in the treatment of sepsis, a disease that kills about 3,500 people every year in the Netherlands alone.
On to BioTrip
Mulder and Netea joined forces with drug developers and biotech investors, so that new technologies actually reach patients. From this is biotech incubator BioTrip to arise. “We don’t want this exciting technology to end up with a nice publication, something that happens regularly in the academic world. Via BioTrip we can translate our research to the clinic. Hopefully, our joint efforts will eventually lead to a treatment that will reduce the high mortality and morbidity rates associated with sepsis,” adds co-author and dean of TU/e’s Department of Biomedical Engineering Professor Maarten Merkx.
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