12 December 2012

Blood Cancer Treatment: Let lymphocytes kill each other

Reprogrammed immune cells saved a seven-year-old American woman from leukemia

Copper newsOncologists from the Children's Hospital of Philadelphia and their colleagues from the University of Pennsylvania presented at the annual conference of the American Society of Hematology in Atlanta the results of the first clinical trials of an experimental method of anticancer therapy for a stable form of acute lymphoblastic leukemia (ALL) – the most common and aggressive type of leukemia in children, according to a press release from the hospital (Leukemia Patient Cancer-Free After Novel Treatment With Engineered Immune Cells).

Thanks to the new method, the authors of the technique managed to achieve stable remission of ALL in a seven-year-old girl.

CART19 or CTL019 therapy was developed at the University of Pennsylvania for the treatment of B-cell leukemia, in particular B-cell chronic lymphocytic leukemia. The essence of the method is to reprogram the patient's immune cells (T cells) in such a way that their target is cancer cells, in this case B cells. A weakened version of the human immunodeficiency virus is used as a vector for the delivery of genetic material when creating modified T cells (chimeric antigen receptors, CART cells). After being injected into the patient's bloodstream, CART cells begin to attack B cells, recognizing them due to a specific CD19 protein that is located on their surface.

Clinical trials of CTL019 therapy are currently being conducted on 12 patients with various forms of B-cell leukemia - ten adults and two children. As the authors of the method reported in their report at the conference, nine of them have a positive effect, and three have persistent complete remission.

Among them is seven-year-old Emma Whitehead, who became the first child with ALL to undergo CTL019 therapy. The disease was diagnosed in the girl in 2010, when she was five years old. Emma was included in the 15 percent of ALL cases that do not respond to existing treatment methods. She had relapses of the disease twice after chemotherapy courses.

In April 2012, at the Children's Hospital of Philadelphia, Emma underwent a course of CTL019 therapy adapted for resistant forms of ALL, and three weeks after the end of treatment, no traces of the disease were found in her. Seven months after treatment, the girl remains in stable remission.

Meanwhile, immediately after the introduction of reprogrammed T cells into her body, Emma began a so-called "cytokine storm" – the extremely active destruction of B cells stimulated an excessive immune response, accompanied by a massive release of immune response regulators, specific cytokine proteins. High levels of cytokines in the blood cause multiple inflammatory reactions in the body tissues, high fever, blood pressure spikes and other life-threatening symptoms. The girl was placed in intensive care, her condition was critical.

However, this reaction was extinguished with the help of a drug commonly used to treat rheumatoid arthritis – tocilizumab, which inhibits receptors for one of the cytokines, interleukin-6, whose level in Emma exceeded the norm by a thousand times. Previously, tocilizumab has never been used for such conditions. Within a few hours after using the drug, the child's condition began to stabilize. The effect that was demonstrated by tocilizumab in Emma's case allowed its mandatory use to be included in the protocol of CTL019 therapy and successfully used in the treatment of several adult patients.

In August 2012, the Swiss pharmaceutical giant Novartis bought the exclusive rights to CTL019 therapy from the University of Pennsylvania and allocated $ 20 million for the construction of a research center on the university campus to bring this method to market. According to Herve Hoppenot, president of Novartis Oncology, quoted by The Globe and Mail (Experimental treatment reprograms patient's own cells to kill cancer), the results already obtained indicate that the proposed method is capable of revolutionizing the approach to the treatment of leukemia and other types of blood cancer. In addition, it opens up prospects for the treatment of malignant neoplasms of other organs.

Portal "Eternal youth" http://vechnayamolodost.ru12.12.2012

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