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T Cell Treatment Could Eradicate Some Forms Of Childhood Leukemia

March 26, 2013

redOrbit Staff & Wire Reports – Your Universe Online

A research team from The Children’s Hospital of Philadelphia and the University of Pennsylvania used a novel cell therapy to reprogram the immune cells of two leukemia patients, resulting in a complete remission of the disease and a total lack of evidence of cancer cells in their bodies.

The treatment, which is described in a study that is currently available online and will appear in the April 18 print edition of the New England Journal of Medicine (NEJM), caused the group of white blood cells known as T cells to multiply at a rapid rate and destroy leukemia cells in the two patients.

One of the patients was a seven-year-old girl named Emily Whitehead. Emily suffered from acute lymphoblastic leukemia (ALL), a form of the disease characterized by excess lymphoblasts. Eleven months after receiving bioengineered lymphocytes, she remains healthy and cancer-free, according to the researchers.

The second patient, an unnamed 10-year-old girl, had a similar response to the treatment initially. However, she suffered a relapse two months later when other leukemia cells appeared — cells which did not harbor a specific cell receptor that it is targeted by the T cells. Both patients were treated at The Children’s Hospital of Philadelphia.

“This study describes how these cells have a potent anticancer effect in children,” said co-first author Stephan A. Grupp, director of Translational Research for the Center for Childhood Cancer Research at the medical facility, in a statement. “However, we also learned that in some patients with ALL, we will need to further modify the treatment to target other molecules on the surface of leukemia cells,” added Grupp, who is also a professor of Pediatrics at the University of Pennsylvania´s Perelman School of Medicine. His co-first author on the study, Michael Kalos, is an adjunct associate professor in the school´s department of Pathology and Laboratory Medicine.

The research is part of the Grupp team´s efforts to develop treatments for B-cell leukemias — forms of the disease that target a specific type of white blood cells responsible for surveillance against disease-causing agents — using modified T cells. They previously had success treating three adult chronic lymphocytic leukemia (CLL) patients, and have now decided to adapt that treatment towards ALL, another form of B-cell leukemia and the most common childhood cancer in the world.

“After decades of research, oncologists can currently cure 85 percent of children with ALL. Both children in the current study had a high-risk type of ALL that stubbornly resists conventional treatments,” the University of Pennsylvania School of Medicine explained. “The new study used a relatively new approach in cancer treatment: immunotherapy, which manipulates the immune system to increase its cancer-fighting capabilities.”

“Here the researchers engineered T cells to selectively kill another type of immune cell called B cells, which had become cancerous,” they added. “T cells are the workhorses of the immune system, recognizing and attacking invading disease cells. However, cancer cells fly under the radar of immune surveillance, evading detection by T cells. The new approach custom-designs T cells to ℠see´ and attack the cancer cells.”

The researchers took T cells from each patient, then altered them in a laboratory in order to create a chimeric antigen receptor (CAR) — an artificially engineered T cell receptor — known as a CTL019 cell. Those cells are specially designed to attack a certain type of protein which is only present on the surface of some types of B cells.

Thus, they hone in on B cells like a type of guided missile, and they rapidly multiply and circulate once returned to the host´s body, making them an effective tool against B-cell leukemia.

However, the process does not come without some side effects. Specifically, when the CTL019 cells are eliminating the leukemia cells, they also could generate an overactive immune response known as cytokine release syndrome.

According to the researchers, this condition can result in extremely high fever, low blood pressure and other side effects. The condition, they said, was “especially severe” in Emily, requiring the medical team at her hospital to administer treatment without harming the cancer fighting effects of the modified lymphocytes.


Source: redOrbit Staff & Wire Reports - Your Universe Online



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