This new technique was posted in Science magazine by a team of American scientists. The investigation demonstrated a rapid and sustained immune reprogramming in animal models, which makes it promising for the treatment of cancer and autoimmune diseases.
Therapies with T cells receiving chimeric antigens (CAR) have been very successful in the treatment of B cell neoplasms, and also have potential to treat autoimmune diseases and blood cancers, such as leukemia and lymphoma.
Generating CAR-T cells requires a lot of time and is very expensive for patients. “You have to extract blood, send it to a central manufacturing laboratory and then return (T cells),” said Carl June, from the University of Pennsylvania, United States.
But to overcome this obstacle, the team, led by Capstan Therapeutics and in which it participates, among others, the University of Pennsylvania, developed a new technique: generate CAR-T cells directly within the organism. For this, directed lipid nanoparticles (TLNP) were used, which directly lead to T lymphocytes a cargo of messenger RNA (RNAm), a type of molecule that transports genetic information.
The use of RNM should avoid the risk of permanent genetic alteration because, unlike DNA -based methods, the MRNA is not integrated into the genome of T cells, explains the Science report.
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THE CHALLENGES OF THE STUDY
An important obstacle in RNM administration with lipid nanoparticles (LNP) is its tendency to be absorbed by the reticuloendothelial system of the liver, which filters the strange particles of the blood torrent. To try to solve this problem, a specific lipid was designed to be used to create lipid nanoparticles aimed at a specific cell protein, called CD5.
When they were tested in mice, rats and monkeys cynomolgus, these directed lipid nanoparticles showed a lower liver capture and a more precise transport towards T cells.
To test the effectiveness of the method, humans blood samples were used with Autoimmune diseases. It was shown that patients derived from patients could be manipulated with an efficacy similar to that of healthy donors, and that patients’ cells could successfully eliminate, which were the objective.
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Results with a promising future
In grafted mouse models with human immune cells, a single dose of TLNP caused, in a matter of hours, a rapid and selective depletion of B lymphocytes, with effects that lasted up to two weeks.
In an experimental model of leukemia xenoinjet, the repeated administration of the TLNP produced an almost complete elimination of the tumor, which underlines the potential of this in vivo approach to treat both cancer and autoimmune diseases, said Science.
The scientists indicated that “by eliminating the requirements of the complex ex vivo manufacturing, this TLNP platform has the potential to make car-T cell therapies more accessible and applicable to other clinical indications.”
(With EFE information)
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