2024-01-04 09:25:35
by Vera Martinella
Some drugs in this category have concluded the last phase of testing for different types of lymphoma and myeloma. The aim is definitive healing
They were the center of attention of specialists from all over the world gathered in San Diego (California) for the annual congress of the American Society of Hematology because, as happened about ten years ago with CAR-Ts, they represent the most recent innovation and improve survival even in patients who have previously had no alternatives.
Bispecific antibodies are called this because they are composed of two parts: one recognizes the target on the surface of the tumor cell and the other binds to a healthy T cell of our immune system, bringing it close to the tumor cell, so the T cell becomes activated and destroys it.
There are already several bispecific antibodies used to treat various types of lymphoma and myeloma, but for now they are only prescribed in the third line (i.e. to patients who have not received the hoped-for benefits from the two previous lines of treatment and whose disease continues, progresses) and mainly to patients participating in trials because for now only one of these drugs (mosunetuzumab) has been officially approved by the Italian Medicines Agency explains Paolo Corradini, president of the Italian Society of Hematology (Sie).
What they are and how they work In practice the bispecific antibody ensures that the body’s natural defenses learn to recognize and destroy cancerous cells – replies Corradini, director of the Hematology Division of the IRCCS Foundation National Cancer Institute of Milan -. at the basis of a new treatment principle, an innovative form of immunotherapy based on T lymphocytes: it effectively creates a sort of bridge between two different proteins, the receptor expressed on the surface of the T cells (those of our immune system) and the one on the surface of cancer cells. In this way the immune system is stimulated to recognize tumor cells and activated to fight them effectively.
Against which tumors are they useful? With regards to haematological neoplasms, several bispecifics have reached the conclusion of phase three trials (the last before the final approval and entry onto the market of a medicine) for patients with B-cell non-Hodgkin’s lymphoma who have not responded to other therapies or have relapsed after receiving them (glofitamab, mosentuzumab, epcoritamab) and myeloma (teclistamab, talquetamab, cevostamab). They are also administered in the third line to patients who relapse after CAR-T immunotherapy, which unfortunately happens in about half of patients with large B-cell lymphoma.
What is the difference with drug-conjugated antibodies?
Drug-conjugated antibodies are also composed of two parts: one acts as a radar and recognizes the target to be hit (i.e. the cancerous cell) while the other carries the load, a sort of very heavy chemotherapy, capable of destroying it. The difference with bispecifics which do not activate the immune system, but destroy tumor cells with a toxin. The therapy is thus directed, in an extremely precise and effective manner, only against the diseased cells and spares the healthy ones. Some of these antibodies are used in lymphomas (brentuximab, loncastuximab) and another in multiple myeloma (belantamab).
What is the difference between CAR-T and bispecific Both treatments activate and enhance the response of our immune system against the tumor, but they do so in different ways. Certainly, CAR-Ts are therapies that involve a more “complicated” procedure (a sort of lymphocyte auto-transplant), requiring hospitalization and can have greater toxicity, while bispecifics are administered intravenously or subcutaneously, with few effects. collaterals which generally tend to disappear after the first infusions. While CAR-Ts are for a single treatment, bispecifics must be taken for many months or until the disease recovers: they are therefore a longer treatment for the patient. Of course, both therapies are very expensive: the bispecific ones have a lower price, but must be administered for a longer duration.
Which strategy gives better results. We don’t know for now, a lot probably depends on the characteristics of the individual neoplasm: we need to study and understand more so that we can better select the patients to whom one or the other treatment is administered. It is important to reiterate that neither of the two approaches excludes the other, therefore a patient who needs it will be able to have the drug-conjugated antibody, the bispecific and the CAR-T. The aim obviously always remains that of definitively curing the disease.
For which pathologies are they already approved? In the United States and Europe there are already numerous antibodies approved and commonly used in hospitals – concludes Corradini -. The Italian Medicines Agency, for now, has granted reimbursement to two drug-conjugated antibodies (brentuximab and belantamab) and a bispecific one (mosunetuzumab). For others it is hoped that the green light will arrive in 2024.
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January 4, 2024 (modified January 4, 2024 | 08:24)
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