The European Medicines Agency (EMA) has approved two drugs that exploit CAR-T cells against two forms of cancer of blood cells. Italy now lacks the approval of the Italian Medicines Agency (AIFA), but in the meantime trials are underway in selected centres, including Humanitas. In the meantime, the possibility of modifying the cells of the immune system of a patient with a tumor is becoming increasingly concrete, so that only diseased cells are multiplied and destroyed, without damaging healthy tissues. We talked about it with Dr. Luca Castagna, Head of Cell Therapies, Haematology, in Humanitas.
A new possibility of treatment against cancer
A new therapeutic possibility, closer and closer, through which modified cells, CAR-T, of the immune system of a patient with cancer are armed, with the mission of selectively destroying the diseased cells. This is how this innovative treatment, still in its experimental phase, works in practice:
1. In the authorised centre, a sample is taken from the patient to isolate his or her T
2. The T lymphocytes are sent to the company that produces the drug, where the gene that codes for the Car that recognizes a specific tumor is inserted.
3. Modified T lymphocytes (CAR-T cells) are returned to the centre and reinfused in the patient.
4. CAR-T cells act by recognizing the cells of that specific tumor and destroying them.
Drug cells for certain non-Hodgkin lymphomas and acute lymphoblastic leukemia
The name that defines this therapeutic approach, by which they are called cells-drug, is CAR-T, an acronym (Chimeric antigen receptor T) that indicates T lymphocytes with a chimeric receptor.
“T lymphocytes are responsible for the human immune system and CAR-T cells are modified T lymphocytes, armed against a single target, specific to a particular disease,” explained Dr. Castagna. “CAR-Ts approved by the EMA for use in humans are directed against the CD 19 protein, which is expressed on B lymphocytes of certain non-Hodgkin lymphomas and acute lymphoblastic leukemia. Therefore, we currently have this new therapeutic possibility only for these two cancers; for all the others it is still necessary to construct T lymphocytes directed against a certain antigen, finding a specific target for each tumour, but there are already studies for multiple myeloma, acute myeloid leukaemias and also in solid tumours”.
From one phase of the trial to the next
“As for any other drug, both ordinary and therefore chemical as these consist of cells, the steps are the same, and it will take at least a few months before they can be used in all patients for whom they are indicated – explained Dr. Castagna, clarifying that the authorization by the EMA on the use of these two treatments does not mean, however, that they are immediately available for all cases in which they may be indicated.
“The companies that produce these cells will have to submit a dossier to AIFA, which will follow the normal path to approve their use in Italy: transpose the directives of the EMA, establish the price and refundability; moreover, being ‘drugs’ made up of cells, it is necessary a regulation, currently not defined, to establish which centers can use them, with what characteristics and quality, also considering the cost that will be high.
Who are the possible patients?
The new possibility, if approved, could affect those who have not yet responded to usable therapeutic schemes: “With regard to lymphoma, which we have followed in Humanitas, the patients who are candidates for the commercial use of this treatment, once the steps of AIFA have been completed, will be those who have had a relapse after various therapies, including autologous transplantation; if instead we consider the clinical trials, which precede the placing on the market, it depends on the type of study that is conducted but in general it includes patients in an advanced stage of disease, who have received different types of treatment”.
The excellence of Humanitas and its effectiveness on lymphomas
In Italy there are few qualified centers, which must demonstrate that they know how to treat the cells taken from patients, know how to treat patients for potential complications of this therapy, have an adequate organization to avoid side effects and offer the greatest possible safety to patients. The choice of centers for these experimental studies is therefore very limited.
“In lymphomas the results of the studies carried out so far are good, although they do not reach 100% effectiveness. Following the administration of CAR-T cells, the disease is reduced in 7-8 patients out of 10 treated and survival is about 50%. This means that at the moment, with a follow up after the therapy still rather short, equal to a little less than two years, half of the patients have remained without disease – said Dr. Castagna -. We are therefore facing an effective therapy: a good step forward, which represents only the beginning, an opportunity in addition to others, on which to work to improve both the effectiveness and tolerance. Meanwhile, to find further solutions and possibilities: “In some U.S. centers there are already CAR-T cells directed against other antigens of cancer cells: if the action against one antigen does not work, try another. Of course it’s still a long way, in the testing phase. In the meantime, even if the attempt with the CAR-T that we now have at our disposal does not work, we do not stop and other therapies will be used, for example transplantation from a donor”.