T-cell therapy against B-cell leukemia
Specialists of the Children's Clinic of Philadelphia and the University of Pennsylvania have achieved remission in two children with an aggressive form of pediatric B-cell leukemia (acute lymphoblastic leukemia) with the help of a new therapy consisting in injecting the patient with his own immune cells reprogrammed outside the body for rapid reproduction and destruction of malignant cells.
The principle of the method is to isolate a certain number of T-lymphocytes of the patient and attach an antibody to the CD19 molecule to their surface. The "chimeric antigenic receptor" formed as a result of this manipulation provides the ability of modified cells to find and selectively destroy B lymphocytes expressing the CD19 molecule on their surface. After being injected back into the patient, these cells divide repeatedly, increasing their population several thousand times, and circulate throughout the body. Moreover, they remain in the body for a long time, protecting it from relapses of the disease.
One of the side effects of therapy is the development of an overly active immune response – the so–called cytokine release syndrome - accompanied by a life-threatening increase in body temperature, a decrease in blood pressure and other undesirable manifestations. However, the relief of these symptoms is possible with the preservation of the antileukemic activity of modified T cells.
Another consequence of treatment is the destruction of healthy B-lymphocytes expressing the CD19 receptor. Therefore, in order to maintain a normal immune status, patients need regular administration of immunoglobulins, which can be carried out at home.
One of the patients, 7-year-old Emily Whitehead, has been in remission for 11 months after the therapy. The second patient, a 10–year-old girl, whose name is not called, had a relapse 2 months after the therapy, the cause of which was the appearance of a new type of malignant cells that do not have a CD19 receptor. Experts believe that this is a consequence of previous attempts to treat the girl using traditional methods.
Currently, researchers are working on improving therapy, one of the goals of which is to reduce the likelihood of recurrence of the disease.
As part of a parallel clinical study, doctors at Memorial Sloan-Kettering Cancer Center in New York injected 5 adult patients with relapses of acute lymphoblastic leukemia with their own T-lymphocytes modified with a therapeutic virus carrier gene that "taught" them to recognize and destroy CD19 receptor expressing B-lymphocytes.
In one of the patients, the symptoms of "incurable" leukemia completely disappeared within 8 days after the start of treatment. The remaining four patients took up to eight weeks to do this. Unfortunately, one of them subsequently died from an unrelated thrombosis, and another from a relapse of the underlying disease.
To date, the three surviving patients are in remission lasting from 5 months to 2 years.
According to experts, they are already preparing for a new clinical trial, in which 50 patients are planned to participate. They are also considering the possibility of applying a new approach to the treatment of other types of cancer. To do this, it is necessary to identify a target molecule (or a combination of molecules) expressed exclusively on the surface of a certain type of malignant cells.
Articles by Stephan A. Grupp et al. Chimeric Antigen Receptor–Modified T Cells for Acute Lymphoid Leukemia and Renier J. Brentjens et al. CD19-Targeted T Cells Rapidly Induce Molecular Remissions in Adults with Chemotherapy-Refractory Acute Lymphoblastic Leukemia are published in the New England Journal of Medicine and Science Translational Medicine, respectively.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of the University of Pennsylvania: T-Cell Therapy Eradicates an Aggressive Leukemia in Two Children and New Scientist: Gene therapy cures leukaemia in eight days.
01.04.2013