In a phase 1 trial at Memorial Sloan Kettering Cancer Centre (MSK), published in Nature Medicine, a new vaccine is being investigated as a potential off-the-shelf treatment in bowel and pancreatic cancer patients with a KRAS mutation.
“Having a vaccine that’s ‘off-the-shelf’ would make it easier, faster, and less expensive to treat a larger number of patients,” says gastrointestinal oncologist at MSK, Dr Eileen O’Reilly, who co-led the trial. “This gives hope for people with pancreatic and bowel cancer who have been out of effective treatments when their disease returns.”
The study involved 25 KRAS-mutated bowel and pancreatic cancer patients at high risk of their cancer returning after surgery. The vaccine was administered after surgery with a view to preventing or delaying recurrence.
KRAS, kirsten rat sarcoma virus, is a cancer-causing gene with a high mutation rate, which is associated with various cancers including pancreatic ductal adenocarcinoma, non-small cell lung cancer, and bowel cancer. Approximately 40% of bowel cancers have a KRAS mutation.
In healthy cells, KRAS functions as an on-off switch that regulates cell growth and survival. When the gene is mutated, KRAS can become stuck in the “on” position, allowing uncontrollable cell growth, which can then lead to cancer.
According to the study results, the vaccine is safe and appears to stimulate the patient’s immune system to create cancer-fighting cells.
84% of patients had the desired immune response, meaning immune T-cells targeting cancer cells with a KRAS-mutation were activated and grew in number.
Also noted in 84% of patients, circulating tumour DNA (ctDNA, a marker for lingering cancer cells) was reduced. In 24% of patients, ctDNA was completely absent.
Patients who had a higher T-cell response also experienced a longer time without the disease returning, known as disease-free survival (DFS).
