Targeting vulnerabilities of childhood cancers

26 April 2023
"NexTGen represents crucial and overdue work” Sara Wakeling, NexTGen team advocate and CEO and co-founder of Alice's Arc

Cancer is the second leading cause of death among children and adolescents worldwide. Yet, despite progress in understanding the biology of many childhood cancers, treatments, particularly for solid tumours, have scarcely advanced over the past 30 years.

Taking on the Solid Tumours in Children challenge, the NexTGen team is developing novel therapies that target unique features, or vulnerabilities, in solid tumours in children.

This article was originally included in our annual progress magazine, Discover: a year of scientific creativity.

“We’ve seen a wealth of research activity for patients with B-cell malignancies,” says NexTGen team co-lead Catherine Bollard of the Children’s National Hospital, US, “but solid tumours, and especially paediatric solid tumours, are still a massive problem, and have not yet garnered the same efficacy as they have for blood cancers.”

Chimeric antigen receptor (CAR) T-cell therapy is a revolutionary cellular therapy that uses specially altered T cells to strengthen the inherent cancer-fighting power of these immune cells. In 2017, the first CAR T-cell therapy was approved for childhood B-cell malignancies. The NexTGen team – co-led by Martin Pule of the UCL Cancer Institute, UK, a world-leader in CAR T-cell engineering – aims to expand the use of this approach in solid tumours, in which success has been limited.

NexTGen investigators are taking a five-pronged approach to exploit the unique vulnerabilities of childhood cancers. They will identify suitable targets for T-cell based therapies; design effective T-cell-engineering strategies to overcome the immunosuppressive tumour microenvironment in childhood cancers; generate T-cell-engineering components specifically for paediatric cancers; use novel modelling methods to test new therapies; and conduct innovative clinical trials.

The team’s multidisciplinary approach – “bringing in people who don’t always speak the same [scientific] language,” as Catherine describes it – includes immunologists, engineers, oncologists and mathematicians, who are learning from one another and finding ways to use their collective expertise to tackle complex problems.

“NexTGen represents crucial and overdue work,” says team advocate Sara Wakeling, CEO and co-founder of the rhabdomyosarcoma network and charity Alice's Arc. “It has hope written all over it. Hopefully, one day, a family who have no idea that they will face a solid tumour diagnosis will be suitable for the innovative treatment devised by our Cancer Grand Challenges team, and their chances of a safe cure will be far better than they are today.”