[LUM#10] Cells Reprogrammed to Fight Cancer
Treating cancer patients by genetically modifying their immune systems is the principle behind CAR-T cell therapy. This revolutionary treatment is already saving lives and opening up new horizons in the fight against cancer.
More than just a new therapeutic approach—it’s a revolution. They’re called CAR-T cells, short for Chimeric Antigen Receptor T-cells. This term refers to a specific type of cell in our immune system: T lymphocytes. But not just any T lymphocytes: these are genetically reprogrammed to fight cancer cells more effectively. Guillaume Cartron, a hematologist at Montpellier University Hospital and university professor, explains.
“A cancer cell is a clever cell: it is capable of deceiving our immune system by expressing proteins on its surface that make it appear to lymphocytes as a normal cell.” As a result, T cells do not recognize it as a cell to be eliminated, so they do not destroy it, and the cancer spreads.
Genetic modifications
To circumvent this mechanism, it was necessary to ensure that T cells could effectively recognize cancer cells so that they could activate upon contact and eliminate them. This is the true feat of CAR-T cells. Researchers have succeeded in genetically modifying these T cells to make them more effective. “Certain cancer cells display a specific antigen called CD19 on their surface, so the 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 through a simple blood draw and sent to a laboratory. There, they are genetically modified: a gene encoding a protein that recognizes the well-known CD19 antigen and a gene that activates the T lymphocyte 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 to produce a large number of these CAR-T cells. “This reprogramming and multiplication process takes about a month, after which the genetically modified T cells are reinfused into the patient, ” explains Guillaume Cartron. They are then able to specifically recognize tumor cells and activate themselves to destroy these malignant cells.
This treatment currently has two specific indications: it is intended for patients with a specific type of lymphoma called “diffuse large B-cell lymphoma” or acute lymphoblastic leukemia. “It is specifically intended for those whose disease is resistant to standard treatments or who have relapsed after intensive treatment, and who have a life expectancy of less than 10%, ” explains the specialist. Thanks to this revolutionary treatment, the cure rate has jumped from less than 10% to about 50%! However, there is a downside: the occurrence of significant side effects that require transfer to the intensive care unit in about 30% of cases.
New therapeutic approach
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 received it. Worldwide, nearly 1,000 patients have been treated with CAR-T cells.
Research in this field is continuing, with the primary goal of genetically reprogramming cells to 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 potential applications,” adds Guillaume Cartron. “We can envision using it against other types of cancer, but also to treat viral infections or certain autoimmune diseases, for example. It’s a new therapeutic concept that has emerged, and the revolution is only just beginning.”
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