Long - playing lymphocytes
CAR-T cells were found in the blood of patients cured of leukemia a decade after administration
Daria Spasskaya, N+1
American researchers — pioneers in the field of CAR-T therapy — published in Nature a report on the condition of two of their former patients who were cured of chronic lymphocytic leukemia after the introduction of CAR-T cells as part of the first phase of a clinical trial of this drug in 2010 (Melenhorst et al., Decade-long leukaemia remissions with persistence of CD4+ CAR T cells). It turned out that functional modified cells are still present in the blood of both participants, who have remained healthy all this time (more than ten years).
The trial referred to in the report included patients with refractory or chemotherapy-resistant leukemia and lymphoma caused by malignant transformation of B cells expressing the CD19 cell marker. As part of experimental therapy, twenty adult patients with different diagnoses were injected with their own T-lymphocytes as medicine, in whose genome the chimeric antigen receptor (CAR) gene against the CD19 protein was embedded. These lymphocytes were supposed to recognize malignant cells and destroy them.
According to the results of the trial, out of 14 patients diagnosed with chronic lymphocytic leukemia, three were completely cured. However, unfortunately, oncological diseases often recur in cured people, so for each experimental therapy it is important to assess how long the patients were in remission, that is, they remained healthy. This is especially important in the case of cell therapy, since immune cells in the absence of an antigen can be depleted or disappear altogether.
Researchers from The University of Pennsylvania under the leadership of Carl June, who conducted tests of their cellular drug CTL019, regularly took tests from cured people, and observed CAR-T cells. Ten years after the treatment, they published data on the state of anti-cancer immunity in two patients (what happened to the third is not reported). In addition to the fact of the presence of modified cells, the researchers were interested in their functional state — which genes they express, which markers they carry, and whether they are able to activate when an antigen appears.
Scientists have discovered an interesting feature in the behavior of CAR-T cells in one of the patients. Shortly after treatment in both people, the cells showed mainly a "killer" phenotype, which is characterized by the presence of the CD8 marker. Nine years later, in remission, in the first patient, CAR-T cells formed a large population with an "auxiliary" phenotype, which is characterized by the CD4 marker. Nevertheless, CD4+ cells isolated from his blood showed cytotoxic activity in vitro when they were cultured together with cells carrying the "cancer" antigen CD19. Apparently, CAR-T turned into some kind of hybrid cells with preserved anti-cancer functionality, which the authors of the work called "an intriguing observation."
CAR-T therapy was officially approved in 2017, when the U.S. Food and Drug Administration authorized its use against leukemia in adults. This type of treatment has made it possible to save many patients with previously incurable types of blood cancer, but in the fight against solid tumors, its success so far remains quite modest. Nevertheless, the approach of gene modification of immune cells is actively being tried in other areas of therapy, for example, for the treatment of fibrosis, HIV or "rejuvenation" of the body.
Portal "Eternal youth" http://vechnayamolodost.ru