CAR-T cells: how to turn your lymphocytes into a medicine

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Welcome to the world of and cellular blood 60th edition of the American Society of Hematology , the American Society of Hematology. The ASH is the world’s most important meeting – nearly 5,000 communications, 25,000 hematologists from around the world – entirely devoted to blood diseases (lymphomas, myelomas, leukemias …). The opportunity for hematologists worldwide to learn about the latest advances in their discipline. Example with including some sustainable obtained with the so-called CART cells, the CART Cells (in English “Chimeric Antigenic Receptor”), a sophisticated approach (see box below) that mixes gene therapy and cellular evoked by more than 700 studies presented at the ASH.

A CAR-T reserved for multiple myeloma, a cancer still incurable, under development

It is already of these ‘living drugs’, living medicines as the Anglo-Saxons call them, have been hailed. Results that are confirmed this year again, with unexpected survival, which often translate into months and sometimes years of extra life where the weeks seemed counted. The few patients involved (barely 100 in the world) all have severe and refractory forms of various forms of leukemia or lymphoma and are at one point in failure with standard treatments. It is indeed to them alone that are reserved these treatments literally built to measure.

“These therapies are unquestionably innovative, ” said Dr. Joseph Alvarnas, moderator of the TAC-AT session at ASH and oncologist at Duarte, California, ” but at the same time we are identifying their limits. effect stop working in some patients. “ This is the reason why the time has come for the introduction of new combinations, associating T-CACs with other immunotherapy molecules. As .

For the moment, only two products, Kymriah (Novartis Laboratories) and Yescarta (Gilead Laboratories), marketed in the United States, are available. In France, both have obtained a temporary authorization for use and are starting to be used in a few patients in ultra specialized centers (Nantes, Rennes, Paris, Lyon, Lille). But already another product, a CAR-T reserved for multiple myeloma, a cancer still incurable, is currently under development in the United States. This new CAR-T says anti BCMA, that is to say directed against the BCMA protein carried by tumor cells and developed by laboratories Janssen and Legend Biotech USA Inc., is in the trial phase and its first results come to be presented at the ASH. Code name is JNJ-68284528. To be continued.

CAR-T cells, what is it?

These are made-to-measure medicines made from the patient’s cells. Here, the strategy is to modify the immune system of patients to teach some of their cells, T cells, to destroy blood tumor cells (see infographic below). It all starts with a venous blood sample to collect the famous T lymphocytes. These are then sent to the United States and genetically modified in vitro to express an artificial receptor, called chimeric , which specifically recognizes the cells. of the tumor to fight. After a delay of about a month, these reprogrammed super T cells, now ready to kill the tumor cells, are reinjected to the patient in a single injection. But these tailor-made treatments remain therapeutic under very high surveillance. Their side effects can indeed be potentially very severe. Like the dreaded “cytokine storm”, occurring in the days following the injection and corresponding to the massive destruction of tumor cells. Lastly, their very high price, several hundred thousand euros per patient, questions the financing capacity of healthcare systems.

The manufacturing process of T-CANS

(Click on the infographic to enlarge)

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