Antibody Therapy for Pediatric Neuroblastoma

A new approach that turns small groups of immune system cells into soldiers that hunt down and kill neuroblastoma throughout the body could save the lives of many children each year, according to researchers.

Neuroblastoma is a cancer that occurs in immature nerve cells and affects mostly infants and children. The disease typically has already metastasized throughout the body by the time the disease is diagnosed.

Scientists at St. Jude Children's Research Hospital (Memphis, TN, USA) utilized a therapy comprised of a combination of T cell antibody to neuroblastoma cells and a molecule to stimulate T cell growth and was created to treat low initial tumor levels or small cancer cell populations that survive initial treatment.

The potential of this therapy is considerable because up to now only 40% of children with neuroblastoma can be cured; children who suffer relapses following treatment are virtually incurable. This study suggests that the immune system can be modified to target cancer cells that have become resistant to conventional 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 department at St. Jude. A report on these preclinical studies was published in the December 1, 2005, issue of the journal Clinical Cancer Research.

The St. Jude strategy represents an advance on a similar method that showed great promise during clinical trials in Germany and elsewhere. Earlier studies with antibodies caused problematic side effects, such as fever and pain, which limited the level of antibody that could be used in the treatment, according to Dr. Barfield, co-author of the study. "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 article's first author. "And many children who are successfully treated suffer a relapse within five years.”

The investigators infused into a laboratory model of neuroblastoma an antibody called hu14.18, which sought out and attached to a protein called GD2 on the surface of neuroblastoma cells. They also infused a specific 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 a synthetic 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 rids itself of this cytokine. The scientists isolated the gamma-delta-T lymphocytes from blood samples taken from healthy human volunteers.

The antibody and the fusion protein Fc- IL7 used in the present study were provided by EMD Lexigen (Billerica, MA, USA).






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