Neuroblastoma is a solid tumor cancer that begins in the nerve tissue of the neck, chest, abdomen, or pelvis but usually originates in the abdomen in the tissue of the adrenal gland.
Neuroblastoma rapidly spreads through the body, making it difficult to treat.
Nearly 70% of those children first diagnosed, have a disease that has already metastasised or spread to other parts of the body. At this later stage (stage IV) it is recognised as “High-Risk”. The average age at diagnosis is two years old.
Prognosis for neuroblastoma is dependent on age, stage of disease, and the molecular biological and cytogenetic characteristics of the tumor. There is very little known about why neuroblastoma occurs, or about what factors increase the risk for occurrence.
High-risk neuroblastoma remains a major cause of death due to malignancy. The majority of high-risk Neuroblastoma patients will experience disease relapse. Once relapse occurs, there is no known cure.
Children with advanced-stage disease, (Stage IV) have a significantly decreased chance for cure despite intensive therapy. This is despite the fact that many patients reach the end of treatment with “no disease detectable”. There are a number of reasons, however, why the disease returns. But the main the reasons appear to be that cancer cells have become resistant to traditional chemotherapy and that microscopic residual disease is still present, although “invisible” on scans, at the end of conventional treatment.
Even following the current protocol of intensive chemotherapy, surgery, radiotherapy and cis-retinoic acid, children with high-risk neuroblastoma have a 2-year survival rate of approximately 20%.
However, a new anti-neuroblastoma antibody is currently under production at St. Jude's to provide an additional tool to destroy residual microscopic disease. The St. Jude's study suggests that the immune system can be manipulated to target cancer cells that have become resistant to traditional chemotherapy.
The St. Jude's strategy represents an improvement on a similar technique that showed great promise during clinical trials in Germany and elsewhere. Prior to this study, antibodies caused troublesome side effects, such as fever and pain, which restricted the level of antibody that could be used in the treatment, However, the antibody used in St. Jude's study appears to be less likely to cause side effects. That suggests that it could be used in humans at higher levels that may improve the effect of the antibody.
Now the technical bit
In the St. Jude's study, 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.
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