Among the new frontiers and perspectives to defeat cancer are the modified CAR-T cells: it is increasingly concrete, in fact, the possibility of modifying the cells of the immune system of a patient with a tumor, so that only the sick cells are multiplied and destroyed selectively, without damaging healthy tissues.

To date, the European Medicines Agency (EMA) has approved two drugs for two forms of cancer of blood cells; in Italy there is still no approval from the Italian Medicines Agency (AIFA), but in the meantime trials are underway in selected centers, including Humanitas.

CAR-T: a specific and armed lymphocyte that fights a certain disease

CAR-T, or Chimeric antigen receptor T, are 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. Luca Castagna, Head of Cell Therapy, Hematology, in Humanitas.

“CAR-T approved by the EMA for use in humans are directed against a protein, called CD 19, which is expressed on the B lymphocytes of some non-Hodgkin lymphomas and acute lymphoblastic leukemia. At present, therefore, we have this new therapeutic possibility only for these two forms of cancer; 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 leukaemia and also in solid tumours”.

The efficacy of T lymphocytes in treating lymphomas

With regard to the treatment of lymphomas “the results of studies carried out so far are good, although they do not reach 100% effectiveness”, explained the professor again. “Following the administration of 2 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, amounting to just under two years, half of the patients have remained without disease. “We are therefore facing an effective therapy: a good step forward, which represents only the beginning, an additional opportunity alongside others, on which to work to improve both its effectiveness and tolerance.

In the meantime, the research does not stop, 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 is 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”, concludes the

Side effects, if any

CAR-T cells are undoubtedly one of the new perspectives in the fight against certain cancers and bring great hope to patients, but as with any treatment, important side effects cannot be excluded. “The side effects are there and are linked precisely to the function of these modified cells – explained the doctor -. They are in fact very active cells that, once recognized the target, proliferate, expand and act by killing the cells, but at the same time producing substances called cytokines. In the case of a widespread disease, with the destruction of a large number of cells, as happens in lymphomas and leukaemias, the significant production of chemicals can give rise to side effects, which are basically the cytokine release syndrome and neurotoxicity, ie a toxicity in the brain. In recent studies that have been done it has been found that many patients have these complications, but it is also true that the serious cases, at an extreme stage, are about 1-2%. So there may be side effects, but now we know how to control them better.

Drug trials and approvals: the next steps

However, the authorisation by the EMA of the use of the two treatments does not mean that they are immediately available for all cases where they may be indicated. “As with any other drug, both ordinary and chemical, and like these made up of cells, the steps are the same, and it will take at least a few months before they can be used in all the patients for whom they are indicated,” clarified Dr. Castagna. “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, a regulation is necessary, currently not defined, to establish which centers can use them, with what characteristics and quality, also considering the cost that will be high”.

A new possibility, therefore, for those who have not responded to the therapeutic schemes that have so far been used: “As far as lymphoma is concerned, which we have followed in Humanitas, the patients who are candidates for the commercial use of this treatment, once the AIFA steps have been completed, will be those who have had a relapse after various therapies, including autologous transplantation; if, on the other hand, we consider clinical trials, which precede the placing on the market, it depends on the type of study being carried out but, in general, patients in an advanced stage of the disease who have received different types of treatment are included”, concluded Castagna.