The findings from this trial are published in the Proceedings of the National Academy of Sciences.
The disease, called X-linked severe combined immunodeficiency (XSCID), is caused by a mutation in a gene called gamma C that prevents the immune system from forming B and T lymphocytes.
XSCID was made famous by the story of the so-called “Bubble Boy” who lived inside a plastic ‘bubble’ to shield him from infections. In gene therapy for this disease, normal copies of the gamma C gene are inserted into stem cells that later give rise to these lymphocytes.
Following the development of leukemia by the patients in France, researchers determined that some of the gamma C genes had inserted themselves into oncogenes – cancer causing genes. This caused the stem cells to multiply uncontrollably and produce leukemia.
The St Jude researchers concluded that XSCID itself makes their mouse models – and by extension, children with this disease – particularly susceptible to cancer caused by gene therapy.
Specifically, the team found that the population of primitive stem cells that is the target of gene therapy is abnormally large. This increases the chance that gamma C genes that are put into the cells will insert themselves into oncogenes.
“Our current findings with this new mouse model offer real hope that we can make gene therapy for X-linked SCID safe as well as effective,” said Dr Yan Shou, the first author of the paper and the major contributor to this work.
Another major implication of this finding is that gene therapy for other forms of genetic blood diseases will pose significantly less risk for causing cancer than was previously thought, according to Dr Brian Sorrentino, director of the St Jude experimental hematology division and co-director of transplantation and gene therapy.