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Gene therapy benefits seen decades after treatment

An international collaboration between Great Ormond Street Hospital, the UCL GOS Institute for Child Health and Harvard Medical School has found that the beneficial effects of gene therapy can be seen decades after the transplanted blood stem cells have been cleared by the body.

Hematopoietic stem cell (HSC) gene therapy

Gene therapy first involves removing some of the patients’ stem cells (can repopulate all blood types and immune cells). Then, experts use a viral vector to deliver a new copy of the faulty gene into the cells’ DNA. These altered stem cells are then transplanted back into the patient (autologous transplant). Here, the cells go on to produce a continual supply of healthy immune cells.

Using integrating viral vectors in HSC gene therapy has enabled researchers to trace the fate of transplanted cells in vivo. This is done by means of integration site clonal tracking. However, to date, no experimental setting has been able to validate that a population of human lymphoid progenitors can survive long-term in the absence of ongoing contributions from HSC.

Long-term progenitors

In this study, published in Nature Communications, researchers monitored five patients who were successfully cured of SCID-X1 using gene therapy. Patients with X-linked severe combined immunodeficiency (SCID-X1) classically present with complete absence of T and NK cells.

The team specifically found that these patients lacked vector-positive myeloid/B cells indicating absence of engineered stem cells. However, they did retain gene markings in both T and NK cells. The researchers found that decades after treatment they were still able to detect vector-positive naïve T cells. Without gene corrected HSC, this T cell production is likely being maintained by a population of long-term lymphoid progenitors.

The team believe that this gene therapy has created the ideal conditions for the human thymus to host a long-term store of the correct type of progenitor cells. Further investigation into this process and identification of these long-term lymphoid progenitors could be exploited to develop next generation gene therapy and cancer immunotherapies.

Image credit: By luismmolina –