New Advancement in Cancer Immunotherapy . The Hospital Clínic has developed a new CAR-T therapy, ARI-0002h, against multiple myeloma resistant to standard treatments. Multiple myeloma is a cancer of plasma cells, which are found in the bone marrow and are an important component of the immune system. It is the first CAR-T developed in Europe for this disease and its results, according to the Clinic, are encouraging: all patients improve with treatment and 75% of them maintain the response at 12 months.
The immunotherapy, which acts on the immune system of the cancer patient, is today the most revolutionary today in the treatment of cancer. There are many types of immunotherapy and one of them is CAR-T cell therapy, which consists of genetically modifying T lymphocytes (cells of the immune system), after drawing blood from the patient, to act against acute lymphoblastic leukemia , lymphoma of B lymphocytes and, now, against multiple myeloma. Myeloma accounts for 10% of bone marrow cancers and is the second most common blood cancer, behind lymphoma.
The Clinic had already developed a first immunotherapy, CAR-T ARI-0001. It was the first entirely manufactured in Europe and this first was indicated for adults over 25 years of age with advanced acute lymphoblastic leukemia. It was also, last February, the first of public origin approved by the Spanish Agency for Medicines and Health Products (Aemps). The Ministry of Health already financed, since 2019, two commercial CAR-T of two pharmaceutical companies, but this was the first public in the world.
Now the Clinic has developed its second CAR-T therapy of public origin, which has had the support of the La Caixa Foundation, which invested five million euros to promote this “pioneering” and “high-impact” research against cancer . The hospital trusts that the Aemps will approve this new treatment “shortly after Easter”.
This Barcelona hospital has also coordinated a multicenter study in various Spanish hospitals to treat patients with multiple myeloma resistant to standard treatments.
Lymphocyte modification
The term CAR responds to the English acronym for Chimeric Antigen Receptor. When this therapy, as is the case, is carried out on T lymphocytes (which are in the blood), then it is called CAR-T. CAR-T is a type of cell and gene therapy in which the patient becomes his own donor. It consists of modifying the T lymphocytes in the patient’s blood so that they have the ability to attack tumor cells.
“This is the second CAR-T that we have developed at the hospital. On this occasion, unlike the ARI-0001, it is directed against another target, BCMA, the most widespread antigen in myeloma immunotherapy,” explains the Head of the Department of Immunology at the Center for Biomedical Diagnosis (CDB) of the Clinic, Manel Juan. Juan also highlights that, within the field of immunotherapy, CAR-T are the ones that “are having the best responses.”
Through apheresis, a technique that allows the separation of blood components, T lymphocytes are obtained, a type of white blood cell responsible for the immune response. These are genetically reprogrammed so that when they are transfused back into the patient, they can specifically recognize the tumor cells and attack them.
“Humanized” essay
This CAR-T is directed against the BCMA antigen , which is found on the surface of myeloma tumor cells. The good results of the research led Aemps to approve the ARI-0002h clinical trial in myeloma patients who had no other therapeutic options. “With respect to the previous CAR-T that we have developed, this one presents a novelty and is that it is humanized. Many times mouse antibodies are used for the development of the CAR-T and in this case we have humanized it so that it has a greater durability in the patient and less probability of rejection “, adds Juan.
The success of this new CAR-T opens the door to treating other types of cancer with this technique . In fact, the Clinic wants to open a CAR-T trial for breast cancer next year. Juan highlights that the fact that the CAR-T developed by the hospital are of public origin also makes it easier to investigate minority cancers.
Essay
“The results of the trial, in which 30 patients resistant to treatment have participated, show that, at 12 months, 75% maintain the response and do not have disease progression, and that 60% have complete remission”, says hematologist Carlos Fernández de Larrea, head of the group on Mechanisms of progression in monoclonal gammopathies at the Institut d’Investigacions Biomèdiques August Pi i Sunyer (Idibaps). Neither has neurological toxicity been seen and the immune adverse effects were mild.
“These results are comparable in efficacy to the commercial CAR-T that exist against multiple myeloma and with less toxicity,” says Álvaro Urbano-Ispizua, director of the Clinical Institute for Hemato-Oncological Diseases . “Now we are preparing all the documentation based on the results to request the use of AEMPS as an advanced therapy drug of non-industrial manufacture,” he adds.
