A conference abstract (not a published paper) presented at American Society of Haematology annual meeting looks at results of a phase 1 clinical trial using base edited cells to treat resistant T-cell leukaemia.
This Roundup accompanied an SMC Briefing.
Prof Simon Waddington, Professor of Gene Therapy, UCL, said:
“There have been some stunning clinical successes with ex vivo gene therapy of autologous cells (namely, cells taken from the patient, genetically modified and then reinjected). However, in this form, the technology will not scale up because every patient essentially provides their own medicinal product.
“In this study, a bank of cells was generated — a single bank of cells which could be used to treat many patients. This enables scalability, commercial viability, and standardisation of the medicinal product.”
Dr Alena Pance, Senior Lecturer in Genetics, University of Hertfordshire, said:
“It is very exciting to see the use of base editors in clinical applications. The high precision and minimal DNA damage of this technology makes it very versatile for gene therapy so a demonstration that it can safely be used to treat human disease is a fantastic development. The strategy of creating universal lines of cells, in this particular case, immune cells, that can be transferred into a variety of patients also constitutes a great prospect for a wider clinical application of gene therapy and stem cell technology.
“Base editors allow precise nucleotide substitutions in the DNA without having to break the DNA to force the cell machinery to repair it and in the process make mistakes, which is the main mechanism of CRISPR-Cas9. This property of base editors and the advances to improve their accuracy means that the exact wanted changes can be made, leaving no trace on the DNA otherwise, reducing the potential of collateral effects. The demonstration that this technology can be safely used in humans brings the possibility of advanced gene therapy, such as correcting disease-causing point mutations closer to an achievable reality.
“It needs to be taken into account that in this particular case, donor cells were modified ex-vivo, then introduced into the patient and finally eliminated once their job was done. On one hand this is a novel therapeutic strategy but it also highlights the challenges still ahead to develop further and wider application of this technology.”
Conference abstract: ‘Cellular Immunotherapies: Early Phase and Investigational Therapies, Trial in Progress: TvT CAR7: Phase 1 clinical trial of base-edited “universal” CAR7 T cells for paediatric relapsed/refractory T-ALL’ by Robert Chiesa Christos et al.
This was under embargo until 00:01 UK time on Sunday 11 December 2022.
There is no full paper and the conference abstract is not peer reviewed.
Dr Alena Pance: “I confirm I have no conflict of interest with regards to this work.”
For all other experts, no reply to our request for DOIs was received.