Bone marrow transplant patients given immune cells with ‘safety switch’

Blood stem cell transplants supplemented with white blood cells engineered to carry a ‘safety switch’ have been given to three patients  at Great Ormond Street Hospital (GOSH). 

The first-in-man study, published in the journal PLOS ONE, showed that the white blood cells could be engineered in the laboratory to stably carry a safety gene that allows cells to be eliminated if they cause side effects. 

The study shows that gene transfer technologies are ready for wider applications, with treatments against certain viruses and cancers set to be tested using the new technology.

In the Phase I/II clinical trial, led by GOSH and the UCL Institute of Child Health (ICH), white blood cells known as T cells were taken from donors and modified to express a ‘suicide gene’ known as TKCD34. The CD34 component allowed engineered cells to be collected and enriched using antibodies fixed to tiny magnetic beads. The TK part made the cells easy to ‘kill off’ at a later date if signs of severe side effects such as graft-versus-host disease (GVHD) developed.  GVHD is a serious complication of bone marrow and stem cell transplants, particularly where tissue matching between donor and recipient is not perfect, and is one of the most difficult challenges faced by patients and their doctors.

The engineered T cells were given to three patients receiving mismatched stem cell transplants after chemotherapy as part of their treatment for blood or immune disorders. Although at the low doses used none of the patients went on to develop significant GVHD requiring the safety switch to be triggered, the patients cleared viruses they were infected with, including one child who had a serious infection with swine flu.

Dr Waseem Qasim, ‎Consultant in Paediatric Immunology at Great Ormond Street Hospital and lead author for the study, says:

“Mismatched transplants in children - where the donor is not a close match for the child - are usually depleted of T cells to prevent GVHD, but this causes problems in terms of virus infections and leukaemia relapse. We wanted to be able to use T cells from mismatched donors for their potent effects against viruses and cancer cells, but with a ‘safety switch' as insurance against unwanted side effects.

“This study opens the door for powerful new therapies that are entering clinical phase testing.”

All of the main therapeutic reagents were produced in London, through collaborations between ICH, GOSH and the Rayne Institute at Kings College London.  GOSH has a core of world-leading expertise in gene-based therapies for inherited immune disorders through the work of Professors Adrian Thrasher and Bobby Gaspar, and these related technologies are now being applied to address more common diseases in both children and adults.