Targeted therapies against immune cells show promise for sepsis
Nanoparticles made of synthetic proteins that eliminate the excess of irritation of the immune system, while stimulating this process at the same time. This innovation allows for the treatment of sepsis, a condition in which the immune system is weakened. Pharmacists from Radboud University Medical Center (Radboudumc) and bioengineers from Eindhoven University of Technology (TU/e) have teamed up to develop and test new nanomedicine, Targeted therapies against immune cells show promise for sepsis.
The results of their research have been published in Nature Biomedical Engineering.
Sepsis is a life-threatening condition in which the immune system becomes dysregulated due to bacteria, fungi, or viruses. This dysregulation can lead to a severe immune response known as hyperinflammation. As a result, the body deteriorates and the organs fail.
At the same time, the immune system can also be weakened; so that he was paralyzed. This is called immune paralysis, so the body no longer fights off infections.
Join Forces
For many years, scientists around the world have searched for an effective treatment for sepsis. The medicine behind such treatment must simultaneously both irritate and paralyze the immune system. However, the big risk is that any medicine for this reaction can cause paralysis.
Immunologists at the Radboudumc center found that in a petri dish with immune cells the cytokine interleukin-4 prevents inflammation, while unexpectedly causing a trained immune system. This anti-inflammatory property can be used to treat sepsis, but it requires interleukin-4 to target immune cells in the human body. Technically, TU/e researchers have extensive experience in developing methods based on new nanotechnology to fight cancer, for example.
Based on their individual research, TU / e bioengineers invented a new approach based on nanotechnology by creating a fusion protein between interleukin-4 and proteins that form nanoparticles and lipid molecules.
Little Things
Researchers have developed a new type of nanomedicine, which consists of small molecules made from natural proteins that interact directly with immune cells. In this case, bioengineers have created a new binding protein of interleukin-4 and another tissue protein that binds to fat cells. As a result, interleukin-4 is delivered directly to immune cells, suppressing the inflammatory response and stimulating the immune system at the same time. Therefore, the immune system is nourished.
Mihai Netea, professor of experimental medicine at Radboudumc: “We know that the protein interleukin-4 counteracts the aggressiveness of the immune system. To our surprise, in a test tube, this protein can also activate trained antibodies in certain immune cells.
The trained immune system is a part of our immune system that has the ability to learn and thus strengthen the immune system. To achieve this in humans, TU/e developed a new nanodicine based on interleukin-4. And it works, the results show. In blood samples from sepsis patients and laboratory animals, the nanoparticles got the immune system back on track.
New Technology
A new use of nanotechnology is that researchers have succeeded in directing interleukin-4 into certain immune cells. Willem Mulder, professor of precision medicine at Radboudumc and TU/e: “We have been developing new proteins by combining tissue proteins for some time. We did the same for interleukin-4. We made it into nanoparticles. By injecting these nanoparticles into the bloodstream, interleukin-4 is delivered to the target cells.
The researchers point out that the treatment has not been tested on patients. A follow-up study is required for this. However, this method is a very new type of immunotherapy, offering new opportunities in the treatment of sepsis, a disease that kills about 3,500 people every year in the Netherlands alone.
About BioTrip
To bring new technologies to the patient, Mulder and Netea have partnered with drug developers and biotech investors to found the BioTrip biotech incubator. “We don’t want this exciting technology to take away from our beautiful books, which are often used in schools. With BioTrip, we have a path to clinical translation. Hopefully, our work and our joint efforts will eventually lead to a treatment that can help reduce the high rate of death and morbidity in sepsis,” adds the author and Dean of Professor Maarten Merkx of the Department Biomedical Engineering at TU/e.
Source: Eindhoven University of Technology
