December 11, 2022

first therapeutic use of base-editing: new phase 1 trial underway of universal CAR-T cells against T-cell leukaemia

Scientists treating patients with T-cell acute lymphoblastic leukaemia have started a new clinical trial in which patients receive ‘ready-made’ universal CAR T-cells.

Healthy donor cells were fitted with a Chimeric Antigen Receptor (CAR) and simultaneously ‘edited’ using new base-editing technology to change individual letters of the DNA code inside T-cells, allowing cells to be used without donor-matching.

This is a world-first application of therapeutic base editing.

The research team have previously used TALENs and CRIPSR/Cas9 technology to treat B-cell leukaemia but this has not been possible for T-cell leukaemia.  Base editing is a technique that allows the additional edits required to target T-cell leukaemia with this technology.

Data will be shared from the first patient in the trial, treated in May 2022.  The patient had previously exhausted all treatment options for relapsed and refractory T-ALL (T-cell acute lymphoblastic leukaemia) including bone marrow transplant.

The trial (https://www.isrctn.com/ISRCTN15323014) aims to treat up to ten NHS patients from across the UK over the next year.  The trial is sponsored by Great Ormond Street Hospital for Children NHS trust and is supported by the MRC, Wellcome and NIHR.  Clinical trial authorisation was provided by MHRA and ethical approval by a gene therapy advisory committee (GTAC).

Journalists dialled in to this press briefing to hear from the scientists running the trial about the science, the methods and the data, and ask any questions. An independent scientist (who is not involved in the trial) will also be on the panel.

Please note that this was not published or peer-reviewed work (there is no journal paper) – it was early data which was then presented at the American Society of Haematology annual meeting in New Orleans.

Speakers included:

Prof Waseem Qasim, Professor of Cell and Gene Therapy at UCL Great Ormond Street Institute of Child Health, and Consultant Immunologist at Great Ormond Street Hospital (GOSH)

Dr Robert Chiesa, Consultant in Bone Marrow Transplant and CAR T-cell therapy at Great Ormond Street Hospital (GOSH)

also joined by Prof Robin Lovell-Badge, Group Leader, Francis Crick Institute – a third-party expert on genome editing, not involved in the trial

This Briefing was accompanied by an SMC Roundup of Comments.