Gene therapy benefits seen decades after treatment

Healthy immune cells are still forming 18 years after blood stem cell transplantation in patients with faulty immune systems, research has found.

In collaboration with Harvard Medical School, Boston, Massachusetts and Great Ormond Street Hospital, London, researchers at University College London (UCL) monitored five patients affected by SCID-X1 – a severe genetic condition that results in the lack of a functional immune system – who had received gene therapy and were successfully cured. The team analysed patients' blood regularly for 3-18 years to detect which cell types were present in their blood. Although the stem cells transplanted as part of the gene therapy were no longer present, the gene-corrected immune cells, called T-cells, were still forming.

'It has been incorrectly thought for some time that someone needs engineered stem cells in the bone marrow to produce new gene-corrected T-cells.' said co-author Dr Luca Biasco from UCL. 'We spent five years testing our hypothesis from every possible angle and we can now confirm that new T-cells can be still generated for decades even in absence of stem cells.'

Gene therapy is an experimental technique designed to introduce genetic material into cells to compensate for defective genes. It works by first collecting some of the patients' blood-forming stem cells, which generate all types of blood and immune cells. Then by using a carrier, called a vector, the genetically-engineered correct gene is inserted into the DNA of the faulty cells in the laboratory. Finally, the corrected stem cells are re-implanted in the patient, where they start producing a continuous supply of healthy immune cells able to fight infections.

The study showed that while the corrected stem cells were cleared by the body, the five SCID-X1 patients remained healthy and continued generating T-cells for decades after the gene therapy treatment. The British-American team suggested that the human thymus – the organ that makes all blood and immune cells – might work as a long-term store of specialised stem cells, also known as 'progenitor cells', that can generate new T-cells.

'When we initially discovered that newly-engineered T-cells were being actively produced in patients many years after receiving engineered stem cells, we were very excited. We had predicted the existence of the long-term store of cells in the thymus that could turn into T-cells, but now we had the proof.' said Dr Biasco.

Published in Nature Communications, the discovery has important therapeutic implications and 'could be crucial for the development of next-generation therapy and cancer immunotherapy approaches.' said Professor Adrian Thrasher, one of the authors of the study.

The team plans to investigate further in order to improve the safety and effectiveness of this technique.