"Reverse vaccination"
How to hide therapeutic protein from the immune system
Researchers from the University of Buffalo (USA) have developed a way to effectively increase the body's tolerance to certain medications that it may perceive as an "enemy". This "reverse vaccination", unlike the traditional one, teaches the immune system not to attack, but to ignore the foreign agent.
Article by Nguyen et al. Rational design of a nanoparticle platform for oral prophylactic immunotherapy to prevent immunogenicity of therapeutic proteins is published in the journal Scientific Reports.
A relatively new class of drugs that are practically indispensable for certain diseases are the so-called therapeutic proteins obtained using biotechnological methods. But the patient's immune system often perceives them as a threat, reacting with the production of specific antibodies. In this case, the medicine becomes not only unsafe, but often ineffective. And alternative treatment at the same time can be very expensive.
An example is Pompe disease, a rare genetic disease in which the enzyme acid alpha-glucosidase, necessary for the breakdown of complex carbohydrates such as glycogen, does not work. Accumulating in cells, glycogen damages muscle and nerve cells. The therapy of the disease consists in taking a recombinant enzyme, but 90% of patients produce antibodies to this protein.
Another example is hemophilia A, a severe hereditary disease associated with a blood clotting disorder. The most famous carrier of this disease was the British Queen Victoria, thanks to whom in the XIX – XX centuries. hemophilia affected many royal houses of Europe. The cause of the disease is a mutation in the gene encoding the protein factor VIII of blood clotting. At the same time, one third of patients produce antibodies to the corresponding therapeutic protein, which negates the effectiveness of therapy.
Usually in such cases, they try to suppress the immune system in order to weaken the action of antibodies. However, American researchers went the other way: to prevent the appearance of antibodies themselves, they treated therapeutic proteins with nanoparticles containing phospholipid phosphatidylserine.
It has previously been shown that this organophosphate compound can change the "perception" of proteins by the immune system. Usually phosphatidylserine is located on the inside of the membrane of a healthy cell, but it turns out to be on the outside when the cell undergoes self–destruction - apoptosis. The output of this molecule outside serves as a "eat me" signal to immune cells-phagocytes. At the same time, a program of "tolerance" to its own proteins is launched inside the phagocyte. Therapeutic proteins treated with phosphatidylserine can also be "masked" under the latter.
In experiments on mice serving as "animal" models of diseases, the researchers proved that such treatment of recombinant therapeutic proteins used in the treatment of hemophilia and Pompe disease reduced the immunological sensitivity of individuals.
Now scientists have developed an effective preparation of nanoparticles with phosphatidylserine (Lyso-PS), which can be taken orally (by mouth). In experiments on mice, taking this medication prevented the production of antibodies against factor VIII in 75% of animals, and also significantly reduced the level of antibodies against acid alpha-glucosidase.
The new development is promising for preventing the immunogenicity of a wide range of protein-based drugs. It is likely that it can be used in the therapy of autoimmune and allergic diseases of humans.
Portal "Eternal youth" http://vechnayamolodost.ru