Gene, stem and cellular therapies - our impact

This theme aims to develop and refine our state-of-the-art infrastructure to enable us to deliver new gene and cell therapies into the NHS. These therapies use molecular tools to specifically edit faulty cells or genetic material, and replace them with functioning versions. These techniques have previously been used at GOSH to successfully treat infants with childhood cancers such as leukaemia.

We aim to build on past successes and develop similar approaches for a wider range of conditions including areas of unmet need such as skin and muscular diseases.

Here you can read about just some of the ways that research from this theme is already impacting the lives of children.

gene stem and cellular therapies

Nearly 100 children in the UK are diagnosed with neuroblastoma annually, a cancer that comes from the nervous system outside the brain. Half of children diagnosed have an aggressive form and receive very intensive treatment including surgery, radiotherapy and chemotherapy. Yet in around half the cancer grows back during or after completion of treatment. For these children a different treatment is urgently needed.

Making immune cells spot cancer

We are developing a new treatment that uses the body’s own immune cells to target the cancer. T-cells are specialised immune cells that patrol our body, seeking and clearing up cells that are infected, for example with a virus. They do this by scanning cells for signs indicating they are no longer healthy, but, in contrast to infected cells, cancer cells can go unnoticed as they often look very similar to healthy cells. To use T-cells as cancer treatment, we reprogrammed them with a detector called chimeric antigen receptor, or CAR for short. The CAR enables T-cells to spot cancer cells and spring onto action, directly destroying cancer cells and alerting other immune cells of the cancer threat.

Learning how to use CAR T-cells to treat neuroblastoma

We developed a CAR that instructs T-cells to recognise GD2, a marker only present on neuroblastoma cancer cells. We showed that T-cells reprogrammed with this CAR were very effective at killing neuroblastoma, leaving healthy cells untouched. Using the expertise in our BRC we started a clinical trial of CAR T-cell therapy for children with neuroblastoma that isn’t responding to standard treatment. We learned how many CAR T-cells we needed to give for them to work effectively against the cancer cells. We found that if enough CAR T-cells are delivered, they multiplied and, for half the patients, shrunk the tumour or removed cancer cells that had spread to the bone marrow.1

Powering up. 

These ground-breaking results show that CAR T-cells can get rid of cancers like neuroblastoma but, after initially responding to this treatment, the cancer cells grew back again. By studying what happened here, we learnt how cancer cells escape CAR T-cell ‘attack’ and developed new CAR-Ts that keep attacking tumours so the cancer won’t come back. Testing these new treatments is very complex and expensive. We are collaborating with a company founded on UCL research, Autolus Therapeutics, to deliver a trial using these new CAR T-cells in 2022.

To read more:

Antitumor activity without on-target off-tumor toxicity of GD2-chimeric antigen receptor T cells in patients with neuroblastoma - PubMed (

Leukaemia accounts for over 30% of all childhood cancer cases and it affects the production and function of blood cells. The most common form of leukaemia in children is acute lymphoblastic leukaemia (ALL), with 800 children diagnosed in the UK every year. Children with ALL have white blood cells that do not function normally, this means they cannot help them fight infection which can cause fatigue as well as joint and bone pain.

A promising new treatment for ALL is ‘CAR-T therapy’, where specific type of a child’s white blood cells, called T-cells, are removed and treated in the laboratory to insert the CAR molecule. When the cells are then given back to the child, the CAR molecule gets rid of cancer cells. However, this can be a costly and invasive process. CAR-T treatment can also lead to life-threatening side effects and the leukaemia often returns as the treated T-cells disappear from the body.

Recent research at GOSH has tackled these issues. We have developed a new CAR molecule that can attached itself to cancer cells more quickly. Professor Amrolia’s team led the world’s first early clinical trial in children showing this new treatment is safe, had reduced side-effects and improved cancer symptoms.

As well as improving outcomes for children with ALL, we have shared this information with a company that was founded on UCL research: Autolus Therapeutics. This means they can run larger studies which are starting to confirm these finding in more patient groups, meaning that our work is going to improve the lives of many people with ALL.

We also know that in some children CAR-T cells are lost over time, this means the treatment begins to fail. Using a genetic barcoding method, we have found a special subset of T-cells that are essential for destroying cancer cells and we hope this will improve future CAR-T therapies.

In parallel, Professor Waseem Qasim led the development of an alternative approach, using ‘off the shelf’ CAR T-cells for immediate clinical studies in any person who needs them.

Professor Waseem Qasim stands in a hospital corridor wearing a grey jumper over a dark blue shirt

The NIHR GOSH BRC has developed regulator-approved facility to scale up the production of these cells. The results of an early clinical trial have shown that these universal cells can successfully treat both children and adults with ALL. This approach means we no longer need to develop personalised cells from each patient, making CAR-T treatments available to more children.

To read more:

Enhanced CAR T cell expansion and prolonged persistence in pediatric patients with ALL treated with a low-affinity CD19 CAR | Nature Medicine

Clonal expansion of T memory stem cells determines early anti-leukemic responses and long-term CAR T cell persistence in patients | Nature Cancer

Genome-edited, donor-derived allogeneic anti-CD19 chimeric antigen receptor T cells in paediatric and adult B-cell acute lymphoblastic leukaemia: results of two phase 1 studies - The Lancet

Severe combined immunodeficiency due to adenosine deaminase deficiency, known as ADA-SCID, is a rare, life-threatening disease that prevents children from living normal lives because their immune system doesn’t work, and they are unable to fight infections. If left untreated, they often die by the age of two.  The usual treatment involves weekly injections of the ADA enzyme until a matched bone marrow donor can be found. Without a bone marrow transplant children require lifelong ADA injections and preventative medicines, and rarely survive beyond childhood.

In genetic conditions like ADA-SCID, the cause of the disease is a faulty gene in the child’s genetic ‘code’ – gene therapy aims to add a working copy of the gene into the patient’s cells to treat or cure these conditions.

To tackle ADA-SCID, teams in our GSCT theme are developing a gene therapy. The treatment takes stem cells containing the faulty gene from the child’s bone marrow or blood, and then uses a harmless virus to carry a working normal copy of the gene into these cells. The treated cells are then returned to the child and, hopefully, these ‘corrected’ cells are accepted and begin to produce a supply of the healthy immune cells that can fight infections.

Gene therapy lab

Early trials using a “gamma-retrovirus” to carry the normal gene caused serious side effects, including occasionally leukaemia. Our team developed a different virus delivery system – a lentivirus - to deliver the gene, as this is more effective and safer. A clinical trial of this gene therapy began at GOSH in 2012 and expanded to include UCLA and NIH in the USA. To date, more than 70 children have received this transformative therapy and in May 2021, highly impressive results from the first 50 patients treated were published. Two to three years after treatment, 48 of 50 children treated have no symptoms of ADA-SCID (>95% effective), are able to have a childhood similar to their school friends and peers, and no longer need to isolate or take preventative medicines.  No patients on the trial had serious side effects and all survived.

BRC support was critical for the success of this project, from preclinical studies to delivering the life-changing gene therapy. If regulators approve this treatment, it could become standard for ADA-SCID, removing the need to find a suitable donor for bone marrow transplant and its related toxic side effects.

To read more:

Autologous Ex Vivo Lentiviral Gene Therapy for Adenosine Deaminase Deficiency | NEJM