Cells reprogrammed to fight cancer

Treating cancer patients by genetically modifying their immune system: that's the principle behind CAR-T cell treatments. This revolutionary therapy is already saving lives and opening up new horizons in the fight against cancer.

More than a new therapeutic concept, a revolution. They're called CAR-T cells, for Chimeric Antigen Receptor T-cells. An Anglicism that designates 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 able to fool our immune system by expressing proteins on its surface that make it look like a normal cell to the lymphocytes. As a result, the T lymphocytes don't recognize it as a cell to be eliminated, they don't destroy it, and the cancer proliferates.

Genetic modifications

To circumvent this mechanism, T lymphocytes had to be able to recognize cancer cells effectively, so that they could activate on contact with them and eliminate them. And that's what CAR-T cells are all about. Researchers have succeeded in genetically modifying these T lymphocytes to make them more effective. " Some cancer cells have a specific antigen called CD19 on their surface, so the T cells are modified 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 test and sent to the laboratory. There, they are genetically modified: a gene including a recognition protein for the famous CD19 antigen, and a gene for activating 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 reprogramming, the T lymphocytes are multiplied to produce large quantities of these CAR-T cells. " This reprogramming and multiplication process takes around 1 month, after which the genetically modified T lymphocytes are reinjected into the patient," explains Guillaume Cartron. They are then able to specifically recognize tumor cells and activate to destroy these malignant cells.

For the moment, this treatment has two precise indications: it concerns patients with a particular lymphoma called "diffuse large B-cell" or acute lymphoblastic leukemia. " It is specifically designed for patients whose disease is refractory 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 can be increased from less than 10% to around 50%! The downside, however, is the occurrence of significant side effects, which in around 30% of cases necessitate a transfer to intensive care.

New therapeutic concept

Montpellier University Hospital is one of 6 French centers authorized to use CAR-T cells, and since January 2019, the hematology team has taken on 11 patients who have benefited from this treatment. In the United States, where this therapy has been in use for 5 years, almost 300 patients have already benefited. Worldwide, almost 1,000 patients have been treated with CAR-T cells.

Research in this field is continuing, with the ambition of using genetic reprogramming 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 possible applications," adds Guillaume Cartron, "in particular against other types of cancer, but also to treat viral infections or certain autoimmune diseases. A new therapeutic concept has emerged, and the revolution is still in its infancy.