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Trial finds new CAR T-cell therapy is effective at killing cancer cells

Early stage research suggests a new version of an immunotherapy called CAR T-cell therapy has fewer toxic side effects and is effective for longer in adults with relapsed B-cell acute lymphoblastic leukaemia (B-ALL), a group who previously had few treatment options available.

There is currently no approved ‘curative’ treatment available for adult patients with relapsed B-ALL. Current treatment is with chemotherapy and the prognosis for these patients is poor.

CAR T-cell therapy programmes immune T-cells specifically to target cancer cells. However, current CAR T-cell therapies have limitations.

Chief Investigator Professor Karl Peggs, Director of the Sir Naim Dangoor Centre for Cellular Immunotherapy at UCLH, explained: “The immune system can become over-activated by the therapy causing a toxic reaction called ‘cytokine release syndrome’. Another consequence of this over-activation is that the engineered T-cells become immunologically exhausted and no longer persist in the patient’s body. This can allow the cancer to relapse.

“These problems are particularly difficult in adults with relapsed B-ALL and consequently there is no licensed CAR T-cell therapy for adults for this type of cancer.”

Creating a second-generation CAR T-cell therapy

To overcome these issues, the new therapy was designed to bind leukemic cells less tightly and for shorter periods of time than other T-cell therapies. 

The scientists hoped this second-generation design would reduce cytokine release syndrome toxicity and allow the CAR T-cells to live in the patients for longer to prevent relapse.

A Phase 1 clinical trial funded by the NIHR Invention for Innovation (i4i) programme and supported by the NIHR UCLH Biomedical Research Centre (BRC) tested this new CAR T-cell therapy in patients. In the trial 20 adult patients with relapsed B-ALL had their T-cells genetically modified to target their cancer cells.

None of the patients had cytokine release syndrome, and the CAR T-cell levels remained high in patients, with persistence evident in three-quarters of patients for around 6 months.

One month after treatment, 85% of the patients were in complete remission. Furthermore, with persistence of the therapeutic cells, half remained in remission after a year. The results have been published in the Journal of Clinical Oncology.

Trial investigator, Associate Professor at UCL Cancer Institute and consultant haematologist at UCLH, Dr Claire Roddie, said: “This new type of CD19 CAR is designed for faster interactions with cancerous cells.

“The results show that the new design allows for the safe treatment with CAR T-Cell therapy to adult patients with relapsed B-ALL. Moreover, this treatment may allow patients to have long-term remissions with no other treatment.”

After the success of this trial, Autolus Therapies, a spin-off company from NIHR UCLH BRC, has initiated the next phase of research, assessing the therapy in 100 adults with relapsed B-ALL in Europe and the United States. This trial will evaluate the response rate to the therapy as well as duration of response and safety.

'I'm so glad that I was able to take part in the trial'

Claire Evans was diagnosed with B-ALL in 2015 and initially went into remission after treatment. In 2019, her leukaemia returned and she was referred to UCLH for inclusion on the CAR T-cell trial.

As of November 2021, it has been 24 months since her CAR T-cell therapy and she remains in remission.

Claire said: “When I relapsed in 2019 the doctors initially treated me with chemotherapy before one of them mentioned CAR-T and I was referred to UCLH who assessed me for participation in their clinical trial.

“As I was deemed suitable, I was able to start CAR-T treatment fairly quickly. Fortunately for me, I didn't have any adverse effects from the therapy.

“I'm so glad that I was able to take part in the trial, it has made all the difference and I'm still here. The initial results from my latest biopsy show no evidence of disease.”