Development of natural killer cell immunotherapy for paediatric rhabdomyosarcoma

Rhabdomyosarcoma (RMS) is a soft tissue cancer that mostly affects children. Current treatments can have serious long term side effects and are not successful at treating high-risk rhabdomyosarcoma (especially when the cancer has regrown or spread around the body).

Rhabdomyosarcoma is especially good at avoiding the body’s first line of defence against cancer – the immune system. It can hide from immune cells or even switch them off. Treatments meant to reactivate the immune system work well for other cancers, but haven’t worked well for rhabdomyosarcoma. Parents and families stress the need for kinder and more effective treatments.

Dr Matthew Blunt’s team at the University of Southampton want to investigate a safer type of immunotherapy called CAR-NK cell therapy. It bolsters the body’s ability to fight cancer by attaching chimeric antigen receptors (CAR), which can bind to cancer cells, to natural killer (NK) immune cells. The resulting CAR-NK cells have the ability to ‘see’ the previously invisible cancer cells and kill them.

The researchers will investigate rhabdomyosarcoma samples to see why normal NK cells aren’t able to effectively fight the cancer. Using their findings, they will design two new treatment approaches to:

1. Activate NK cells that are already present in these children to destroy their cancer cells.
2. Generate billions of NK cells from healthy adult donors that can rapidly destroy cancer cells once given to patients.

These treatments will be tested in the laboratory using cutting‑edge 3D models of rhabdomyosarcoma grown from real patient tumour cells.