Antibody Therapy Promising for Pediatric Neuroblastoma
News Dec 22, 2005
A strategy that turns small populations of immune system cells into armies that track down and kill neuroblastoma throughout the body could save the lives of many children each year, according to investigators at St. Jude Children's Research Hospital.
The St. Jude study suggests that the immune system can be manipulated to target cancer cells that have become resistant to traditional chemotherapy.
The investigational therapy comprises artificial antibodies that tag neuroblastoma cells, immune cells such as T lymphocytes that attack those tagged cells, and proteins called cytokines that stimulate the T lymphocytes, according to Raymond Barfield, M.D., Ph.D., an assistant member of Hematology- Oncology at St. Jude.
A report on these preclinical studies appears in the December 1 issue of Clinical Cancer Research.
The St. Jude strategy represents an improvement on a similar technique that showed promise during clinical trials in Germany and elsewhere.
Prior antibodies caused troublesome side effects, such as fever and pain, which restricted the level of antibody that could be used in the treatment, said Barfield, co-author of the Clinical Cancer Research paper.
"However, the antibody we used in our laboratory study appears to be less likely to cause side effects," he said.
"That suggests that it could be used in humans at higher levels that may improve the effect of the antibody."
"Our success with this therapy is especially important because neuroblastoma rapidly spreads through the body, making it difficult to treat," said Mario Otto, M.D., Ph.D., a postdoctoral research fellow at St. Jude, the paper's first author.
"And many children who are successfully treated suffer a relapse within five years."
The researchers infused into a laboratory model of neuroblastoma an antibody called hu14.18, which sought out and bound to a protein called GD2 on the surface of neuroblastoma cells.
They also infused a special type of T lymphocytes called gamma-delta T cells, which attacked the cancer cells that were tagged by hu14.18.
To stimulate the gamma-delta cells' growth and activity, the researchers infused an artificial protein called Fc-IL7.
IL-7 is a cytokine - a protein that promotes T-lymphocyte survival and proliferation. The Fc protein (immunoglobulin) that is fused to IL-7 slows the process by which the body disposes of this cytokine.
The researchers isolated the gamma- delta-T lymphocytes from blood samples obtained from healthy human volunteers.