Researchers at Great Ormond Street Hospital for Children (GOSH) and UCL Great Ormond Street Institute of Child Health (UCL GOSH ICH) have used new technology to engineer T-cells to treat seriously ill children.
The first phase of the trial, published in Science Translational Medicine, is said to be “the first use of ‘universal’ CRISPR-edited cells in humans and represents a significant step forward in the use of gene-edited cells for cancer treatment.”
The CRISPR technique involves making a cut in the cell’s DNA, which allows researchers to insert a brand-new genetic code. Researchers can then allow the T-cells to express a receptor, called a chimeric antigen reception (CAR), that can recognise makers on cancer cells and destroy them.
GOSH have noted that although a number of CAR T-cell therapies are now provided by the NHS, they rely on collecting and engineering a patient’s own cells, which is expensive and not always feasible over a short period of time. In this trial, GOSH describe how their team “manufactured their banks of donor CAR T-cells using a single disabled virus to transfer both the CAR and a CRISPR guidance system, and then applied cutting-edge mRNA technology to activate the gene editing steps.”
The CRISPR technique was then used further to edit T-cells so that they can be used without the need for donor matching. The researchers are investigating how donated cells can be pre-manufactured and used in multiple patients in order to reduce costs and make treatments more accessible.
Speaking of the impact of this new research, Dr Kanchan Rao, bone marrow transplant consultant at GOSH said “This study adds to the growing body of evidence that genome-edited T cells can be a viable alternative to currently available treatments.”
The trial involved six children aged 14 months to 11 years, who had relapsed; all of the children had previously undergone standard UK treatments for B-ALL but their disease had returned multiple times. They were given edited cells through an intravenous infusion with treatment remaining active for around four weeks. When successful, patients were then eligible to have a bone marrow stem cell transplant. Four of the first six children entered remission within 28 days, with two of those children remaining in ongoing remission nine and 18 months after treatment, respectively.
Lead author of the study, Professor Waseem Qasim, spoke of the future for the trials like this: “Whilst there are challenges to overcome, this study is a promising demonstration of how emerging genome-editing technologies can be used to tackle unmet health needs in some of the sickest children we see.”
