Combination of T cell, antibody to neuroblastoma cells and molecule that spurs T cell growth is designed to treat low initial tumor levels or small cancer cell populations that survive initial treatment, according to St. Jude.
A new 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.
Neuroblastoma is a cancer that arises in immature nerve cells and affects mostly infants and children. The disease often has already spread throughout the body by the time the disease is diagnosed.
The St. Jude strategy represents the successful translation of concepts into a combination therapy that proved effective in laboratory models of neuroblastoma; and that now includes the production of the drugs made to the high standards required for human clinical trials, the researchers say.
Translating this kind of research into the clinic is important because today only 40 percent of children with neuroblastoma can be cured; children who suffer relapses following treatment are virtually incurable. The St. Jude study suggests that the immune system can be manipulated to target cancer cells that have become resistant to traditional chemotherapy.
"This is an extraordinary model for advancing the field of pediatric oncology," said Raymond Barfield, M.D., Ph.D., an assistant member of Hematology-Oncology at St. Jude. "We were able to make rapid progress by doing all the development and production of the antibody on campus. Now we're planning to submit a proposal to the Food and Drug Administration to begin a Phase I trial of this strategy that will permit us to begin exploring ways to use this antibody technique to treat children with neuroblastoma."
The investigational therapy comprises artificial antibodies that tag neuroblastoma cells, immune system cells such as T lymphocytes that attack those tagged cells, and proteins called cytokines that stimulate the T lymphocytes. 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 great promise during clinical trials in Germany and elsewhere, according to Barfield, who is a co-author of the Clinical Cancer Research paper. Prior antibodies caused troublesome side effects, such as fever and pain, which restricted the level of antibody that could be used in the treatment, Barfield said. "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."
The St. Jude team showed that their treatment could trigger a sustained, highly targeted immune system attack on disseminated (spread over a large area) cancer cells in laboratory models. Moreover, the treatment can be readily transferred to the clinic because each of the three parts of the treatment can be produced at St. Jude at a quality suitable for use in humans, the researchers said.