Breakthrough discovery in cancer research
Scientists have discovered the existence of mutations inherent in all cancer cells of the patient, this increases the effectiveness of immunotherapy and can make it even more personalized
Marina Astvatsaturyan, Echo of Moscow
The principle of targeted cancer immunotherapy is to mobilize cells of the immune system, T-lymphocytes, to destroy specific tumor cells.
In one of the latest issues of the journal Science, the results of a study have been published, which showed that, despite the extraordinary variety of mutations occurring in malignant tumor cells in one organism, each patient has mutations common to all his cancer cells, and thanks to them, an attack on cancer through T cells of the immune system can become a win-win. (McGranahan et al., Clonal neoantigens elicit T cell immunoreactivity and sensitivity to immune checkpoint blockade.)
As the tumor grows, more and more new unique genetic disorders appear in different parts of it, which make themselves felt by peculiar marks on the surface of cells, these new marks are neoantigen proteins.
After analyzing the data of hundreds of patients with lung cancer, the authors of the publication – British oncogeneticists working under the auspices of Cancer Research UK and Rosetrees Trust charities, identified neoantigens representing the earliest cancer mutations. It turned out that they are present on absolutely all tumor cells, and not only in some of their varieties, that is, they are clonal - they originate from the first mutated cell.
But most importantly, scientists were able to isolate specialized immune system cells, T–lymphocytes, from the samples of two patients, which are able to recognize these clonal tags.
In the body, T-cells do not show their destructive potential, because they are turned off by the protective mechanisms of the tumor. However, the discovery itself suggests the possibility of therapy by specifically activating these immune system cells taken from the patient, cultured and targeted at the identified common neoantigens in order to destroy all tumor cells at once.
In the course of the study, another important circumstance became clear: the genetic complexity of cancer with many neoantigens is a property of branched tumor development, but those mutations common to all cancer cells in question arise at the very beginning, in the so–called stem part.
Researchers believe that it is the offshoots with their genetic diversity that allow the tumor to become resistant to drugs. Therefore, according to one of the authors of the publication – Professor Charles Swanton from University College London (see the UCL Tumours contain the seeds of their own destruction press release) - the "Achilles heel" of complex cancer types are precisely stem antigens, it is to them that the immune system cells should be directed first of all.
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