Researchers at the Francis Crick Institute, in collaboration with Revolution Medicines, have shown that a combination of treatments in mice with lung cancer allow immunotherapies to target non-responsive tumours.

Their findings show that targeting tumours in different ways simultaneously might increase response to treatments.

The researchers combined a newly identified KRAS G12C inhibitor with a compound that blocks a protein called SHP, which inhibits cancer cells and can also activate tumour immunity.

These two inhibitors were combined with an immune checkpoint inhibitor, which blocks proteins that help the cancer cells hide from the immune system.

In mice with functional immune systems, the triplet combination shrank the tumours and, in some mice, fully eradicated them. These mice were also more resistant to the lung cancer coming back after treatment.

The team believe that these targeted compounds provide a window of opportunity where the immune checkpoint inhibitor can kick into gear and allow the body’s natural defences to attack the tumour.

Even in mice with ‘immune cold’ tumours that are normally unresponsive to immunotherapy, the combination allowed tumours to become sensitised to the immune checkpoint inhibitors.

Julian Downward, Principal Group Leader of the Oncogene Biology Laboratory at the Crick, and co-senior author with Miriam Molina-Arcas, said: “Blocking genes like KRAS in lung cancer has led to some exciting new developments, but we still see problems with resistance. We’ve now been able to report partial or complete eradication of tumours in mice by combining KRAS and SHP2 inhibitors with immunotherapy. We also showed that this combination therapy allows ‘immune cold’ tumours to respond to the body’s own defences.”

Diana Spencer, Senior Digital Content Editor, DDW