Autolus CAR-T cell therapy gives hope for aggressive blood cancer patients

UCLB spinout Autolus has delivered highly promising results in treating patients with an aggressive blood cancer through a new chimeric antigen receptor T cell (CAR-T) therapy. 

The treatment for relapsed/refractory B-cell acute lymphoblastic leukaemia (r/r B-ALL) demonstrated results in a clinical trial led by researchers at UCL and UCLH. The FELIX trial, sponsored by Autolus Therapeutics and published in the New England Journal of Medicine, showed how a second-generation CAR-T cell therapy, known as obecabtagene autoleucel (obe-cel), has reduced immune toxicity and persists for longer in patients – overcoming two common limitations of earlier CAR-T cell therapies. 

What is B-ALL is how has it been treated? 

r/r B-ALL1 is a type of acute leukaemia which if left untreated causes bone-marrow failure and death. Standard treatment is with chemotherapy and bone marrow transplant, but for most adult patients the leukaemia doesn’t respond to treatment or relapses. These patients are left with few treatment options and poor long-term survival. 

CAR-T cell therapies, which reprogramme a patient’s immune cells to attack cancer, are transforming the treatment of blood cancers. 

In the UK, a CAR-T cell therapy called brexucabtagene autoleucel (brexu-cel) was licensed for relapsed B-ALL in 2023. However, brexu-cel causes high rates of severe cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, side effects caused by over-activation of the immune system. 

In addition, brexu-cel CAR-T cells persist for only a short period of time in patients’ bodies, leaving patients susceptible to relapse. 

UCLB’s Director of Biopharm, Rick Fagan welcomed the trial results: “This promising new therapy is emerging as a real hope for patients suffering from this deadly blood cancer. UCLB has supported Autolus in protecting and licensing the CAR-T technology, and in doing so has helped attract capital to fund its development. The promising result is a great example of a real-world impact emerging from industry and academics working together.” 

Obe-cel solves problems with existing CAR-T cell therapies 

For the FELIX trial, patients had their T cells genetically modified with obe-cel. This treatment programmes immune T cells to make an artificial protein called a CD19 chimeric antigen receptor (CAR) on their surface, directing them to specifically recognise cancerous cells. 

Obe-cel was designed by scientists from UCL Cancer Institute, led by Dr Martin Pule, to address some of the limitations of current CAR-T cell therapies. 

By reducing the time obe-cel CARs engage with their target, Dr Pule hypothesised that obe-cel would cause less inflammation while clearing leukemia cells and allow the CAR-T cells to persist for longer in patients, thereby preventing relapse. 

Obe-cel was licensed by UCLB spinout Autolus Therapeutics following promising data in UCL Phase I studies in children and adults with treatment-resistant B-ALL. 

The FELIX phase 1b-2 clinical trial assessed the safety and effectiveness of obe-cel in adults with treatment resistant B-ALL. 

In total, 127 adult r/r B-ALL patients whose cancer had not responded to treatment or returned after treatment took part in the study at hospitals in the UK, Europe and USA. 

The results showed that 74.7% of patients had a remission after treatment. 

Using the trial data, the team estimated that after six months 65.4% of patients with r/r B-ALL would be alive and disease free if they received obe-cel, with 49.5% alive and disease free after 12 months. 

Further, just 2.4% of FELIX trial patients had severe cytokine release syndrome, compared to around 24%, who received brex-ucel2. 

Severe immune effector cell-associated neurotoxicity syndrome, which occurs in 25% of patients treated with brexu-cel, was experienced by just 7.1% of trial patients who received obe-cel. 

Obe-cel was recently approved by the US Food and Drug Administration (FDA) based on the results of the FELIX trial. 

Dr Claire Roddie, lead investigator of the FELIX trial from UCL Cancer Institute and UCLH, said: “While we have a licensed CAR-T therapy to treat r/r B-ALL in the UK, high toxicity is an issue in around a quarter of patients and lack of CAR-T persistence in the blood can lead to relapse and the requirement for more lines of therapy, including stem cell transplant. 

“In contrast, our results from the FELIX study demonstrate that obe-cel can induce durable remissions with substantially fewer toxicity issues, which is great news for patients with what has historically been a very difficult cancer to treat.” 

Autolus Therapeutics is a UCLB spinout founded by Dr Martin Pule which has raised over $1bn, with most of this invested in the UK. Licensing of obe-cel is currently being sought from the Medicines and Healthcare products Regulatory Agency (MHRA). 

Dr Martin Pule, from UCL Cancer Institute and UCLH, who is also founder and Chief Scientific Officer of Autolus, said: “Success in developing obe-cel shows what can be achieved through collaboration between UCL, its affiliated hospitals and industry.” 

Obe-cel, now known as Aucatzyl,  will be manufactured at Autolus’ commercial manufacturing site in Stevenage, UK, which will supply the therapy globally. 

 

Image credit: Autolus