Introduction

CAR-T therapies have revolutionised cancer treatment, especially for tumours that originate in blood cells such as leukaemias and lymphomas. They involve genetically engineering lymphocytes (the immune system cells responsible for destroying tumours) with a kind of radar or detector that helps them find and destroy cancer cells. 

One of the most common leukaemias, and one that has benefited greatly from the emergence of CAR-T cells, is acute lymphoblastic leukaemia, especially in children. However, although more than 85% of children improve with the therapy, or even achieve complete remission, relapses are very common, and only 50% of these patients survive more than one year after treatment. 

There are two main reasons for this. First, the molecular detectors introduced into the lymphocytes identify only a single molecule on the surface of tumour cells (in the case of acute lymphoblastic leukaemia, this is called CD19). If, over time, the tumour cells hide this molecule from their surface, the lymphocytes can no longer detect them, and the therapy stops working. 

Secondly, these molecular detectors send a powerful signal to the lymphocytes when they encounter a tumour cell, causing the lymphocyte to attack and destroy it. However, it has been shown that such a strong signal can overstimulate the lymphocytes, causing them to become exhausted quickly and, once again, the therapy stops working. 

Unless these two problems are solved, survival rates for children treated with CAR-T will not improve. For this reason, the clinical trial led by Dr Persis Amrolia aims to tackle both issues with current CAR-T therapies in order to prevent relapses. 

The Project

In this clinical trial, Dr Persis Amrolia’s team will treat 12 patients using special CAR-T cells that have been modified in two ways: 

• They do not only recognise one tumour molecule (CD19), but also a second one (CD22). This means that if tumours hide one of them, the therapy may still continue to work.  

• They do not send such a strong signal to the lymphocytes when they encounter tumour cells. This means the lymphocytes are not overstimulated, do not become exhausted as quickly, and can continue working for longer.  

With this trial, major progress is being made in refining therapies that are changing the way cancer is understood and treated. 

Recent Progress

Dr Amrolia’s team has been completing all the requirements necessary to begin the clinical trial and enrol patients. Any therapy that is to be used in humans for the first time must meet a range of prior requirements, submit extensive documentation, and be approved by the relevant regulatory agencies and ethics committees. 

For example, among many other things, they had to demonstrate on three separate occasions that they were able to produce the therapy under high-quality conditions, ensuring that the treatments given to children are always created as accurately and precisely as possible. After exhaustive work, all the necessary approvals have now been secured, allowing the project to begin. 

Thanks to this approval, Dr Amrolia’s team has been able to open the trial and begin treating the first patients. So far, two children with high-risk leukaemias who had not responded to several previous therapies have already joined the trial. Over the course of the year, the team hopes to continue helping patients with these aggressive leukaemias and to report the first results of the trial.