Great Ormond Street Hospital (GOSH) reported a breakthrough application of gene-editing late in 2015 after a team led by NIHR-funded Professor Waseem Qasim and Professor Paul Veys treated an infant with an otherwise incurable form of leukemia.
That experience, and success in a second infant, has now been published in Science Translational Medicine. The cells had been manufactured in the highly-specialised, BRC-supported clean room facility, in collaboration with Dr Martin Pule at University College London Hospital and French Biotech company, Cellectis. This is the most sophisticated version of gene edited cells made to date using TALEN technology.
These gene-edited cells, called CAR-T cells, can effectively induce remission of acute lymphoblastic leukaemia (ALL). However, in some patients – especially infants – it can be hard to manufacture and modify cells directly from the patient. Alternatively, it may be possible to use donor cells from matched allogeneic haematopoietic stem cell donors. In 2015, the team at GOSH used modified T cells from donors, called UCART19 cells, for the first time in humans to treat two infants with extremely aggressive forms of ALL. This treatment led to successful induction of remission which then allowed an allogeneic stem cell transplantation to go ahead.
Over 12 months later both patients are doing well, and the successful application of this technology provides a demonstration of the potential of gene-editing strategies for engineered cell therapies. However, the investigators remain mindful of residual risks of graft-versus-host disease and the likelihood that in some patients the leukaemia will inevitably ‘escape’ immune effects. Phase I trials are underway and aim to treat ten further infants in combination with bone marrow transplantation as part of a company sponsored trial at GOSH. Meanwhile, Professor Qasim’s group, again with BRC support, are moving rapidly to produce the next generation of universal T cells using the next form of gene-editing technology, CRISPR/Cas9.
This work was also highlighted in the Independent.