Synthetic interleukin
Interleukin-2 is a key regulatory protein of the immune system. It is used in the treatment of autoimmune diseases, and is also a potential anti-cancer agent. However, the side effects of its use significantly limit the use of this protein in therapy. The anti-cancer properties of interleukin-2 are due to its ability to activate certain immune cells, in particular, having beta and gamma receptors on its surface. However, natural interleukin-2 also activates cells carrying alpha receptors, which can lead to disastrous consequences, such as increased toxicity and suppression of immunity. To date, all approved therapy regimens using interleukin-2 lead to the activation of these cells.
On January 10, in the journal Nature, a group of scientists from the University of Washington published the results of their study on computer modeling and testing the properties of a substance with similar anti-cancer properties, but without side effects such as interleukin-2.
The protein obtained by computer modeling was named Neo-2/15 – it can also mimic the action of interleukin-15, which, similar to interleukin-2, is considered in a number of studies as a potential substance for chemotherapy.
The Rosetta program developed in the laboratory of the head of the study, David Baker, was used for modeling. The scientists' task was to model a structure that could bind to interleukin-2 receptors of beta and gamma types, but would not bind to alpha-type receptors. To do this, first of all, compact proteins were developed that act as a framework that would hold binding sites with the right receptors in the correct positions. Then the amino acid sequences of the "framework" were optimized, resulting in a protein that is completely different from the natural interleukin-2. Neo-2/15 was tested on a mouse model of rectal cancer and melanoma, showing excellent therapeutic activity compared to interleukin-2. The toxicity was significantly lower.
This study shows that the development of proteins "from scratch" can help in obtaining biocompatible molecules with improved therapeutic properties with the least number of side effects based on almost any biological molecule whose structure is known or can be predicted.
Article by Silva et al. De novo design of potential and selective mimics of IL-2 and IL-15 is published in Nature.
Anastasia Poznyak, portal "Eternal Youth" http://vechnayamolodost.ru / based on the materials of UW Medicine: Scientists design protein that prods cancer-fighting T-cells.