A revolution for the treatment of rheumatoid arthritis. It could come from the results of an Italian-German research published in ‘Nature Medicine’ and signed by the group of Professor Maria Antonietta D’Agostino, director of the Uoc of Rheumatology of the Agostino Gemelli University Polyclinic Foundation Irccs and professor of Rheumatology at the Catholic University, and by Professor Georg Schett, of the Friedrich-Alexander University of Erlangen-Nuremberg (Fau).
The study explored a new possible therapeutic approach to this autoimmune disease, which consists in organizing a sort of blind date between B cells and T cells, the two protagonists of the immune response. The meeting ends with the elimination of the diseased B cells (i.e. those that produce the antibodies responsible for the inflammation and destruction of the joints) by the suppressor T cells. Organizing this sort of ‘immune ambush’ is blinatumomab (or Blina), an immunotherapy already used for the treatment of some blood tumors. In the case of rheumatoid arthritis its use is experimental, but in this research it has obtained an extraordinary and unprecedented effect in terms of therapeutic results.
“In the six patients with multi-treatment-resistant rheumatoid arthritis (including an Italian patient), to whom Blina was administered on a compassionate and experimental basis – explains D’Agostino – the drug produced a rapid decline in the activity of disease, reducing the level of circulating antibodies and improving the inflammation of the synovial tissues, as we documented on ultrasound, Fapi-Pet-Tac and with the transcriptomic analysis of the inflammation of the synovial membrane. The therapy was very well tolerated : Patients had only a temporary rise in temperature at the first infusion, but no signs of cytokine release syndrome.” Sophisticated laboratory analyzes (such as high-dimensional flow cytometry) have confirmed that the clinical improvement is due to an immune reset, consisting in the elimination of ‘bad’ B cells (i.e. with the memory ‘activated’ to continuously produce self- antibodies), which are replaced by ‘good’ B cells.
“These results, very promising for the extent of the response and the tolerability of the drug – comments D’Agostino – suggest the potential usefulness of this therapeutic approach in the most severe forms of rheumatoid arthritis, resistant to therapy. It could be the beginning of a new era of treatment for other autoimmune diseases mediated by B cells, from lupus to scleroderma. The T-cell engager pathway to destroy B lymphocytes, producers of auto-antibodies, which maintain the state of disease activity and are responsible for the failure. response to the drugs currently used, could therefore lead to a new way of attacking autoimmune diseases, exploiting the action of our own immune system, the same concept used by CAR-T therapy, in which T lymphocytes are ‘activated’. to destroy self-reactive B lymphocytes”.
Blina is a bispecific, i.e. ‘two-armed’ monoclonal antibody, a form of immunotherapy that causes the destruction of B cells by suppressor T cells, facilitating their encounter. In short, it is a ‘facilitator’ drug, which brings these two categories of cells closer together, making the elimination by T lymphocytes more effective against ‘deviant’ B cells, i.e. with the memory blocked in the uncontrolled production of antibodies directed against the joints, in the case of rheumatoid arthritis.
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