[LUM#10] Reprogrammed cells to fight cancer
Treating cancer patients by genetically modifying their immune system is the principle behind CAR-T cell therapy. This revolutionary therapy is already saving lives and opening up new horizons in the fight against cancer.
More than just a new therapeutic concept, it's a revolution. They are called CAR-T cells, which stands for Chimeric Antigen Receptor T-cells. This term refers to a certain category of cells in our immune system: T lymphocytes. But not just any lymphocytes: these are genetically reprogrammed to fight cancer cells more effectively. Guillaume Cartron, hematologist at Montpellier University Hospital and university professor, explains.
"A cancer cell is an intelligent cell: it is capable of deceiving our immune system by expressing proteins on its surface that make it appear normal to lymphocytes." As a result, T lymphocytes do not recognize it as a cell to be eliminated, they do not destroy it, and the cancer proliferates.
Genetic modifications
To circumvent this mechanism, it was necessary to ensure that T cells effectively recognized cancer cells so that they could activate upon contact and eliminate them. This is where CAR-T cells come in. Researchers have succeeded in genetically modifying these T cells to make them more effective. "Some cancer cells have a specific antigen called CD19 on their surface, so T cells are modified to enable them to recognize this antigen and then destroy the cancer cell, " explains Guillaume Cartron.
In practice, the patient's lymphocytes are collected from a simple blood sample and sent to a laboratory. There, they are genetically modified: a gene containing a protein that recognizes the famous CD19 antigen and a gene that activates T lymphocytes are incorporated into their genome. This is the principle of immunotherapy: "we take the best of our immune system and modify it to fight a target more effectively, " explains the hematologist.
Destroy malignant cells
After this reprogramming, the T cells are multiplied in order to obtain a large quantity of these CAR-T cells. "This reprogramming and multiplication process takes about one month, after which the genetically modified T cells are re-injected into the patient, " explains Guillaume Cartron. They are then able to specifically recognize tumor cells and activate to destroy these malignant cells.
This treatment currently has two specific indications: it is for patients with a particular type of lymphoma called "diffuse large B-cell lymphoma" or acute lymphoblastic leukemia. "It is specifically intended for those whose disease is refractory to conventional treatments or who have relapsed after intensive treatments, and who have a life expectancy of less than 10%, " explains the specialist. Thanks to this revolutionary treatment, the cure rate has risen from less than 10% to around 50%! However, there is one caveat: the occurrence of significant side effects, which in around 30% of cases require transfer to intensive care.
New therapeutic concept
Montpellier University Hospital is one of six French centers authorized to use CAR-T cells, and since January 2019, the hematology team has treated 11 patients who have benefited from this therapy. In the United States, where this therapy has been in use for five years, nearly 300 patients have already benefited from it. Worldwide, nearly 1,000 patients have been treated with CAR-T cells.
Research in this field is continuing, with the particular aim of carrying out genetic reprogramming that would limit the side effects observed. The second objective is to use CAR-T cells to treat other diseases. "This first gene therapy has many other possible applications," adds Guillaume Cartron. "In particular, we can envisage using it against other types of cancer, but also to treat viral infections or certain autoimmune diseases, for example. This is a new therapeutic concept that has emerged, and the revolution is only just beginning."
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