A baby girl in the UK has been cleared of leukaemia following compassionate treatment with an experimental therapy which used gene-edited cells. It is the first time a therapy using the gene-editing technology TALENs (transcription activator-like effector nucleases) has been used in a human. Previously only tested in mice, the treatment was given on compassionate grounds when the baby girl did not respond to existing treatments. The unpublished results will be presented at the American Society of Hematology in December.
The conference abstract is available here. The media release from the Great Ormond Street Hospital in the UK is here.
For those journalists with a login, the report and any associated materials are available on Scimex.
Feel free to use these quotes in your stories. If you would like to speak to an expert, please don’t hesitate to contact us on (08) 7120 8666 or by email.
———–
Professor Peter Koopman is from The University of Queensland’s Institute for Molecular Bioscience
“This treatment is an astonishing example of the power of gene editing technology. Blood diseases are especially suitable for this type of treatment – the relevant cells can be readily obtained from the patient, are already separated (as opposed to being relatively inaccessible in a solid organ), can be modified and amplified, and replaced where they need to be. Time will tell how widely this kind of treatment can be used for diseases affecting other organs.
Genome editing technologies can sometimes cause unintended changes in the DNA in addition to the desired change. A particularly clever aspect of the way this treatment was designed is that some time later, the engineered cells can themselves be removed from the body, virtually eliminating the already small risk that those cells themselves may cause adverse effects.”
———–
COMMENTS FROM THE GENETIC EXPERT NEWS SERVICE ( a US service based on the SMC focusing on genetics)
Dr. Mark Osborn, Assistant Professor, Department of Pediatrics, Division of Blood and Marrow Transplantation, University of Minnesota
“This first in-human use of TALEN engineered cells is designed to fill a critical gap for the treatment of acute lymphoblastic leukaemia, the most common type of childhood cancer that has a poor prognosis. This study merged genome editing technology with an existing immunotherapy, whereby T cells are engineered to have receptors on their surface, called chimeric antigen receptors (CARs), which recognize and target tumour cells. Previous CAR-based therapies have utilized a patient’s own cells which means treatments have to be individually manufactured.
To standardize the procedure and create a universal treatment, Qasim and colleagues employed TALEN-based genome editing. TALENs function as ‘molecular scalpels’ that cut DNA and inactivate a target gene. The group targeted two genes: one involved in formation of the T-cell receptors and another that sensitizes cells to a monoclonal antibody.
“By disrupting the T-cell receptor, the modified cells are greatly diminished in their propensity to initiate graft-versus-host disease, a complication in tissue or cell transplants which can destroy healthy tissue. De-sensitizing the engineered cells to the monoclonal antibody (mAb) Alemtuzumab allowed the cells to persist in the presence of the mAb, and resist being recognized and removed by the patient’s own T-cells.
The employment of engineered nucleases can result in so called ‘off-target’ effects where similar sequences in the genome to the intended targets are also cleaved. Rigorous assessment of off-target effects will be needed to streamline further patient application. In an elegant approach to account for any deleterious effects of the engineering process, the authors included a ‘suicide gene’ that allows for selective removal of the TALEN/CAR modified cells.
This ‘off the shelf’ approach allows for the generation and banking of a population of cells that can be delivered to any patient for widespread and urgent use. This approach resulted in molecular remission of the leukaemia in this patient and serves as a springboard for clinical trials.”
———–
COMMENTS FROM THE UK SMC
Dr Yalda Jamshidi, Senior Lecturer in Human Genetics, St George’s University Hospital Foundation Trust, said:
“Gene editing is an exciting scientific advance with potential to treat many human genetic diseases. The GOSH/ICH group have successfully edited donor immune T cells using a genome editing technology using tool called TALENs, and used it to treat a young patient with leukaemia who didn’t respond to chemotherapy. Importantly, unlike recent controversial reports of gene editing in human embryos with another technology (CRISPR/Cas9), modifications made to the T cells should not be passed on to future generations. The results of the current study are very promising, and further work needs to be carried out to show long term efficacy, confirm lack of toxicity of the engineered cells and applicability to a wider patient population.”
———–
Dr Simon Waddington, Reader in Gene Transfer Technology, UCL, said:
“There has been recent work by several groups in Europe and the US using gene therapy tools to modify patient T cells to treat cancer; many have yielded very promising results. However this report is exciting for two reasons.
“Firstly, conventionally, gene therapy has been used to deliver extra copies of genes to cells which have no working copies – slightly inelegant although it has worked in quite a number of clinical trials. This new case describes the use of gene editing technology (in this case TALENs) to carefully, and specifically modify existing genes – taking genetic medicine to a new level of precision.
“Secondly, the researchers have used this technology to create an off-the-shelf, generic cell therapy, rather than one specifically tailored for an individual patient. Therefore this could reduce the cost and complexity of the treatment, and ultimately bring benefit to a wider patient population. Nevertheless, this is a very early report and the researchers will now rigorously scrutinise the long-term safety and efficacy of the treatment so more work has yet to be done before this is a technology available to all.”
———–
Dr Matt Kaiser, Head of Research at Bloodwise (previously Leukaemia & Lymphoma Research), said:
“Survival rates for this type of childhood leukaemia are thankfully now high, but there remains a desperate need for less toxic drugs and new treatments for the minority of patients who cannot currently be cured. The concept of training immune cells to specifically recognise and hunt out leukaemia cells is very exciting and in theory could provide a lifetime cure for these children.
“There have been other cases of children who are still in remission after years of receiving similar experimental treatments, but the technique is still in the very early stages of development. This new type of ‘off-the-shelf’ T-cell therapy could represent a significant advance. The next step needed is for it to be tested in larger clinical trials. We need to establish whether it can offer a long-term cure, whether there are any side effects and which patients are most likely to benefit from it.”
———–
Declared interests
· Dr Yalda Jamshidi: “I have no interests to declare.”
· Dr Simon Waddington: “I have collaborated with Adrian Thrasher in the past, and I know Waseem Qasim, Kimberly Gilmour and Martin Pule. I am also based at UCL.”
· Dr Matt Kaiser: No interests to declare.
