Unprecedented success of Blood cancer cell therapy
The experimental personalized therapy with modified T-lymphocytes, called CTL019, developed by researchers at the University of Pennsylvania under the leadership of Professor Stephan Grupp, allowed 90% of adults and children with repeatedly relapsed or unresponsive to standard treatment with acute lymphoblastic leukemia (ALL) to go into remission.
The production of personalized "killer" CTL019 cells begins with the isolation of the patient's own T-lymphocytes using apheresis (a method based on differences in size, deposition rate on filters and other differences in cells during centrifugation). Subsequently, these cells are reprogrammed using the gene transfer method. The resulting modified T-lymphocytes contain an antibody-like protein known as the chimeric antigen receptor (CAR), selectively binding to the CD19 antigen expressed on the surface of B-lymphocytes, including malignant ones. Such T-killers are injected into the patient's bloodstream, where they multiply and attack malignant lymphocytes. The signaling domain included in the CAR stimulates the rapid reproduction of modified cells injected into the patient, which allows each of them to form more than 100,000 new T-lymphocytes.
To date, 25 children and young adults (5-22 years old) who were treated at the Philadelphia Children's Clinic and 5 adults (26-60 years old) who were treated at the University of Pennsylvania Clinic have participated in the clinical study of the new method. The introduction of the cellular drug brought 27 out of 30 patients (90%) into complete remission. After 6 months after treatment, 78% of patients remained alive.
19 of the participants in the clinical trial are currently in remission, 15 of them have not undergone any additional treatment, including a 9-year-old girl who was the first to undergo an injection of modified cells more than 2 years ago.
The follow-up period for the study participants ranged from 1.4 to 24 months and in most cases exceeded 6 months. 5 patients dropped out of the study for alternative therapy, including 3 of them who underwent allogeneic hematopoietic stem cell transplantation during remission. Relapses developed in 7 patients within 1.5-8.5 months after treatment, in 3 cases leukemia transformed into CD19-negative, against which the modified cells are powerless.
All study participants developed cytokine release syndrome within a few days after the introduction of CTL019, which is the main indicator of the start of proliferation and antitumor activity of modified cells. In 22 out of 30 patients, the syndrome was mild or moderate and manifested with flu-like symptoms of varying severity, including fever, nausea and muscle pain. 8 patients developed severe forms that required interventions aimed at increasing blood pressure and eliminating breathing difficulties. The immunosuppressive drug tocilizumab was administered to 9 patients, blocking the effects of the pro-inflammatory cytokine interleukin-6, the level of which sharply increased during the most active reproduction of modified cells in the body. 6 patients also underwent short courses of steroid hormones to suppress the symptoms of cytokine release syndrome. As a result, complete recovery from this side effect of therapy was registered in all patients.
A blood test of the study participants who went into complete remission showed that simultaneously with the tumor cells, the therapy destroyed all normal B lymphocytes carrying CD19 antibodies on their surface. Moreover, the stable absence of these cells indicates a long-term vaccine-like effect of therapy, preventing the recurrence of the tumor. However, given the important role of B-lymphocytes in the fight against infectious agents, patients usually need replacement therapy with immunoglobulin preparations to maintain normal immune function of the body.
In general, the results obtained indicate that the new method of personalized cell therapy is a viable alternative for the treatment of patients with acute lymphoblastic leukemia resistant to treatment or relapsed after stem cell transplantation, as well as for patients without compatible donors.
In July 2014, treatment with CTL019 became the first personalized cell therapy method recognized by the U.S. Food and Drug Administration (FDA) as a breakthrough therapy. The first multicenter clinical trial of this approach has recently begun in the USA, and several additional clinical trials are planned to begin by the end of the year.
Article by Shannon L. Maude et al. Chimeric Antigen Receptor T Cells for Sustained Remissions in Leukemia is published in The New England Journal of Medicine.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of the University of Pennsylvania:
Personalized Cellular Therapy Achieves Complete Remission in 90 Percent of Acute Lymphoblastic Leukemia Patients Studied.
20.10.2014