Blood Cancers : a revolution in the treatment with gene therapy

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Published the 11.12.2017 at 19: 10

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Keywords :

lymphomeCAR-T cellthérapie gene

The most important information of the american congress of hematology is the demonstration that it is possible to use a new technology that had heretofore been rather experimental CAR-T cells in several specialized centers across the world.
This is the first multicenter study with this technique. It has been performed in patients suffering from B lymphoma diffuse large cells in the failure of treatment with lymphocytes “re-educated” to be directed against a target on the surface of malignant cells, the CD19. The study is jointly published in a reputable medical journal, the New England Journal of Medicine. But other diseases and other forms of CAR-T cells can be detected.

A long progression in the treatment of blood cancers

Up to now, to destroy malignant cells, it was necessary to poison them while leaving the sick to survive.
This task was facilitated by the fact that malignant cells multiplying faster than the other, absorbing more chemotherapy than healthy cells and also because physicians preparing associations of molecules chemotherapy who were more likely to be toxic to cancer cells and their specific mechanisms.
Marrow transplants have also been developed where it was to destroy all the bone marrow with chemotherapy, dose-intensive and then to replace it with a cord brand new.
But a new step has been taken in recent years with the advent of targeted therapies. It was primarily a matter of specific antibodies developed as soon as the research was a new target on the surface of diseased cells, a target which should be as specific as possible to the cancer cells and the least specific of normal cells.

The CAR-T cells are derived from gene therapy

But the antibodies have a limited lifespan, the researchers then turned to the task of developing immune cells capable of attacking cancer cells that carry these same targets.
And they then used genetic research to incorporate into the genome of T-lymphocytes the ability to develop a surface antibody capable of directing itself on the targets previously identified as being specific to different cancer cells.
This involves taking T-cells from patients, transferring the gene that will secrete antibodies specific surface area of the disease through a viral vector which will integrate this gene in the genome of these cells to edit them, and then grow these cells and reinject.
So, it is a mini-autologous lymphocyte cells modified T of the sick so that they attack specifically cancer cells. The 2 problems of CAR-T cells are the time, the whole procedure takes 15 days to 3 weeks, and the cost, the whole treatment would cost a minimum of $ 500,000.

Extension of the domain of the fight

Initially developed in acute leukemia in children, CAR-T cells specific for different blood cancers of adults (myeloma, lymphoma, etc.).
The edition 2017 of the american congress of hematology, the ASH 2017, is the congress of the confirmation for the CAR-T cells in different forms of leukemias.
The multicenter study cited above was conducted in severe and resistant B lymphoma large cell. This is BECAUSE T-cells, anti-CD19, a marker expressed on the surface of B cells of burkitt’s lymphoma. She was concerned 147 patients in 22 centers throughout the world, of which 99 have received the treatment. The genetic modification and the cultivation of T-lymphocytes of these patients has been centralised in a single centre in the USA, then in Switzerland, before the pocket of T-lymphocytes in frozen is returned to the hospital where was treated the patient concerned.
In this study, all went well in spite of the multiplicity of centres. Almost all patients were able to have a CAR-T cells, anti-CD19, and the result is outstanding : the response rate was 53% and 32% of the patients are in complete remission at 3 months and 30% at 6-month follow-up. Fifty-eight percent of patients had side effects related with this treatment as a syndrome of release of cytokines, and 21% had a neurological complication inflammatory. But, all these problems have been managed by ad hoc, and no deaths related to treatment is reported.

Other CAR-T cells promising

In myeloma, another CAR-T cell with a specificity anti-BCMA, has been developed in myeloma refractory to all treatment, with excellent results again.
Other CAR-T cells, anti-CD19 are developed by different companies with different skills in terms of aggression and / or duration of life. And this is the 2nd advantage of CAR-T cells : in addition to their formidable effectiveness, these cells have a long life with the ability to eradicate cancer cells, even if they reappear after several months or years. The oldest patient treated with this technique has been there are now more than 7 years ! The cells remain in the body of the patient and are ready to act as soon as the smallest cell of the cancer reappears.
Finally, another promising lead is presented to this congress, and aims to reduce the cost of this technique and its complexity. It is to stop doing the “tailor-made” and almost ” ready to wear “. An allo-CAR-T cell anti-CD19 has been created to be compatible with the most of patients with lymphomas b-lymphocytes that have been modified are no longer just a patient but another patient and there is a conditioning to avoid reactions of the immune system against these foreign cells. Once their task depletion of cancer cells have been completed. A bone marrow transplant is performed to consolidate the results of which are promising, even if it is a preliminary study.

The sick continue to suffer and the treatment remain heavy, but the CAR-T cells represent more than a hope of cure in patients in failure of any treatment, as the first CAR-T cells, anti-CD19 is already marketed in the USA and soon in Europe in the B cell lymphoma to large cell after failure of conventional treatments.