Gene therapy of leukemia
Success again
Now 25 children (up to 22 years old) and 5 adults have already taken part in the tests.
The doctors reported the results in an article recently published by the New England Journal of Medicine (Maude et al., Chimeric Antigen Receptor T Cells for Sustained Remissions in Leukemia). It can already be said that the trials are extremely successful: 27 out of 30 patients had complete remission, 19 are still in remission, and 15 out of 19 patients did not need additional treatment for this. To realize how outstanding this result is, we must remember that people who are not helped by standard approaches decide to participate in clinical trials. Among the participants in the trial was, for example, a patient with a four-fold relapse. There were also those who were not helped by bone marrow transplantation, and those who could not be transplanted due to their current condition.
Acute lymphoblastic leukemia is an oncological disease, like any oncological disease, its mechanism is that some cell in the body begins to divide uncontrollably, quickly and indefinitely. As a rule, this is due to the occurrence of one or more mutations in the cell that disable the division control mechanisms. In the case of lymphoblastic leukemia, a dividing cell is a cell of the immune system – a lymphocyte. Lymphocytes are formed from stem cells and mature in the lymph nodes gradually. Stem cells can divide much faster than mature lymphocytes, so cells that have lost control at earlier stages produce much more dangerous tumors.
The action of the immune system in humans (and in general in all more or less developed species) is largely based on events occurring on the surface of the cells of the immune system. For example, T-lymphocytes get acquainted with fragments of viruses and bacteria presented on the cell surface and then can kill the pathogens themselves. The Philadelphia method of combating leukemia is based on the fact that T-lymphocytes obtained from a patient are taught to recognize not viruses or bacteria, but any B-lymphocytes. This is possible due to the fact that almost all B-lymphocytes carry the same CD19 receptor on the surface. Accordingly, patients with leukemia of B-cell origin were selected for the tests. For some time after treatment, there are no B-cells in the patient's body at all, and in order for their immunity to continue to protect them from infections, they are separately injected with a set of the necessary synthetic antibodies.
Emily Whitehead's website says she feels great now, only coughs at night and suffers from a chronic runny nose. Perhaps this is a consequence of the absence of B cells in her body, but there are 10-year-old children who have the same problems, and B cells are in place. She leads a normal lifestyle, studies in the fourth grade and passes medical checks from time to time. During the last check, she was told that the number of trained T-lymphocytes is decreasing, and in the next six months they may disappear altogether. Then the moment of truth will come. As long as trained T-lymphocytes are present, there are no B-cells, and there is no disease caused by them. When B cells start to appear again, the disease may also return. In some patients, the trained T-lymphocytes disappeared a couple of months after treatment, and all of them had a relapse. Emily's trained lymphocytes will live in the body for almost three years, or even more, and it is with this that doctors pin their hopes that the disease will not return. Therefore, until the B cells have returned, doctors are talking only about remission, not about cure.
If the disease returns, then this is not a death sentence. The course of treatment can be repeated further if necessary, if each time the trained lymphocytes will circulate for several years.
A total of 30 people have participated in the study to date. Of these, 27 had complete disappearance of B cells. However, not everyone had it for a long time. Trained T-lymphocytes disappeared in several patients and the disease returned. These patients died of the disease. Among them was the one who became a participant in the trials during the fourth relapse of the disease. Another patient died from myelodysplastic syndrome – the inability of bone marrow stem cells damaged by chemotherapy to maintain hematopoiesis.
None of the patients died directly from therapy, although the so-called "cytokine storm" begins in the body immediately after the introduction of trained lymphocytes. In some particularly severe cases, such as Emily Whitehead's, he required resuscitation and artificial lung ventilation. It occurs due to the fact that trained lymphocytes consider B-cells to be an infection, begin to fight them and secrete cytokines into the blood – inflammatory mediator molecules. In response to this, a condition develops, as with a very severe infection. However, after Emily's treatment, the doctors were ready for such a turn of events, and after a few days all the patients felt fine.
Of the 19 patients in remission, four underwent bone marrow transplantation after lymphocyte therapy. Another patient, in whom not all malignant cells had CD19 receptor, combined this approach with chemotherapy.
The danger is the occurrence of CD19-negative tumor clones under the influence of therapy. Some chemotherapeutic drugs are also directed against CD19, and their use may increase the selection pressure and, thereby, the likelihood of CD19 clones. Theoretically, for the treatment of such cases, it is possible to develop T-lymphocytes that react to some other surface molecule, but so far there are none.
At this stage, the test results can be assessed as very good. In the group of 30 people actually sentenced to death, 63% are in remission.
Portal "Eternal youth" http://vechnayamolodost.ru05.11.2014