Over the past 30 years, there has been very little improvement in survival rates for children and young people with solid cancers. Now, a global team of researchers is setting out to change that. 

A pioneering trial from Cancer Grand Challenges team NexTGen is testing whether their cutting-edge new therapy can help treat children and young people with solid tumours by harnessing the immune system.

NexTGen is an international team co-funded by Cancer Research UK, the National Cancer Institute in the US and The Mark Foundation for Cancer Research. The team includes researchers across the UK, US and France, collaborating to explore new ways for a type of immunotherapy called CAR-T cell therapy to help children and young people.

The team’s new trial in the UK, MIGHTY, will test CAR-T cell therapies specifically designed for children and young people with sarcomas.

Breaking barriers 

CAR-T cell therapy is a highly advanced and personalised cancer treatment. It works by taking a patient’s own immune cells, called T cells, and altering them in the lab so they can better recognise and destroy cancer cells. This approach has been transformative for people with certain blood cancers, but it doesn’t work for everyone and has faced problems when it comes to other cancer types.

Treating solid tumours with T cells is especially challenging. Unlike blood cancers, solid tumours form dense lumps, which can create a physical barrier to drugs and immune cells trying to reach the tumour cells. These tumours can also change the environment around them, known as the microenvironment, to help them hide from the immune system or weaken the immune cells trying to stop them.

The NexTGen team is developing new ways to tackle this challenge. They’ve developed a new way of modifying T-cells to withstand the tumour microenvironment and recognise a protein called B7-H3, which is found on most solid tumours in children and young people. Recognising this protein allows the T-cells to bind to and kill the cancer cells.

Difficult tumours are not the only problem children and young people with cancer face. Children and young people have far fewer treatment options available to them, and most of these treatments are designed for adults which can cause harsher side effects in younger bodies.

“Cancers in children and young people are fundamentally different from those in adults,” said Dr Karin Straathof, member of the NexTGen team and Lead Investigator for the MIGHTY trial. “They are unique in how they develop, how they resist treatment, and where their vulnerabilities lie. So, the treatments should be different too.

“We urgently need to shift away from simply repurposing adult cancer drugs and focus on developing treatments specifically for younger patients – interventions that not only improve survival but also protect their long-term quality of life. We’re looking forward to seeing the results of this important study.”