New Therapy for Leukemia

Cancer researchers have developed a three-step process in which human leukemia cells and neighboring immune-system T cells are manipulated together in the laboratory to create a specific cancer-killing cocktail. The details of this approach, known as adoptive immunotherapy or cellular therapy, are reported in the October 2002 issue of the journal Biology of Blood and Marrow Transplantation.

"For reasons that are not yet entirely clear, leukemia cells fail to trigger immune responses,” said the paper's senior author, Edward D. Ball, M.D., of the Rebecca and John Moores University of California, San Diego, Cancer Center (USA). "We have developed a method in which we induce the leukemia cell to change its behavior and stimulate the immune system. At the same time, we persuade the immune system to wake up and attack only the leukemia cells.”

A team led by Dr. Ball obtained blood samples from 12 patients with acute myeloid leukemia (AML) at the time of diagnosis or relapse. The researchers simply separated out the white cells, which included the AML cells and the T lymphocytes. Then the researchers added certain growth factors, called GM-CSF (granulocyte-monocyte colony-stimulating factor) and IL-4 (interleukin-4), to the cell mix, turning the AML cells into strong antigen-presenting cells, called dendritic cells. These surface antigens are like red flags to T cells, stimulating them to attack.

Eight days later, the researchers discontinued the GM-CSF and IL-4, and began a 10-day course of IL-2, which is the main T cell growth factor. Following that, they added anti-CD3/anti-CD28 monoclonal antibodies, which are known to amplify the proliferation of T cells.

"By day 42, we saw that the T cells had more than tripled in volume and had killed significant numbers of the patient's leukemia cells,” said Dr. Ball. We also tested this three-step process against cell lines for AML and other types of cancer such as breast and lung cancer. There was a strong killing effect in the AML cell line, but not in the others. This is a very specific action.



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