2019-09-15 20:11:39
One of the most exciting advances produced in the fight against cancer is the generation of “killer” T lymphocytes with chimeric receptors against some molecule characteristic of a tumor. “Killer” T lymphocytes are the class of lymphocytes capable of killing cells in the body that have rebelled against it, such as tumor cells. Tumor cells are abnormal and have abnormal molecules on their surface that can be detected by receptors on “killer” T cells. When this happens, these lymphocytes trigger a mechanism that allows them to secrete various molecules towards the tumor cells, and only towards them, which lead to their death.
However, in their fight for survival, some tumor cells evolve and “learn” to camouflage themselves or even prevent the action of “killer” T cells. The tumor may have been initially slowed down, but not removed. In this situation, generating “killer” T cells with chimeric receptors may be useful. The chimeric molecule contains a receptor part for a molecule characteristic of the tumor cells and another activator part that leads the “killer” T lymphocytes to secrete toxic molecules that will end the life of the tumor cells.
These “killer” T cells with chimeric receptors, called T-cellsCAR, have been used with some success to treat various classes of tumors. However, one of the most difficult to treat are glioblastomas, extremely malignant tumors of the glial cells of the brain, for which effective therapy remains lacking after decades of efforts to achieve it.
Researchers at Harvard Medical School have been able to generate T-lymphocytesCAR capable of detecting a molecule characteristic of glioblastomas. However, not all tumor cells were killed. Some “learned” to stop producing the oncogenic molecule and replace it with another alternative molecule, also a growth activator that was also present in healthy cells, which made it very difficult to use it as an antitumor target, since attacking it would also mean attacking life. of the healthy cells that possess it.
The researchers carried out a second and very ingenious genetic modification in the T-lymphocytesCAR: made them able not only to detect the first oncogenic molecule, but also to produce antibodies against the second molecule.
So far, scientists have used these T-lymphocytesCAR in laboratory animals and have shown that they have potent antitumor activity against glioblastoma. However, several years of clinical studies will be necessary before this technique can be made available in the most advanced hospitals.
Reference: CAR-T cells secreting BiTEs circumvent antigen escape without detectable toxicity. https://dx.doi.org/10.1038/s41587-019-0192-1
Jorge Laborda. September 15, 2019.
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