New KRAS-Targeting Cancer Vaccine Safe, Immunogenic in Trials
Off-the-shelf vaccines are as efficacious as mRNA vaccines and are cheaper to produce and administer
A new vaccine shows encouraging early results as a potential off-the-shelf treatment for certain patients with pancreatic or colorectal cancer, according to a study co-led by researchers at Memorial Sloan Kettering Cancer Center (MSK). The vaccine targets tumors with mutations in the KRAS gene, a driving force in many cancers.
This cancer vaccine is different from another type of pancreatic cancer vaccine, which is custom-made for each patient using mRNA. Both are therapeutic vaccines given after surgery to prevent or delay the cancer from relapsing in high-risk patients. “Having a vaccine that’s ‘off-the-shelf’ would make it easier, faster, and less expensive to treat a larger number of patients,” says medical oncologist and pancreatic cancer specialist Eileen O’Reilly, MD, who helped lead the trial and is one of the corresponding authors in the study published in Nature Medicine. “This gives hope for people with pancreatic and colorectal cancer who have been out of effective treatments when their disease returns.”
Clinical trial results with the KRAS vaccine
The Phase 1 trial involved 25 patients whose pancreatic or colorectal cancer had certain KRAS mutations and were at high risk of cancer returning after surgery. The results demonstrated this vaccine is safe and appears to stimulate the patient’s immune system to create cancer-fighting cells.
84 percent of patients had the desired immune response, meaning that T cells targeting KRAS-mutated cancer cells were activated and grew in number.
Also in 84 percent of patients, cell-free tumor DNA (ctDNA) was reduced. In 24 percent of patients, the ctDNA was completely absent.
Most significantly, patients who had a higher T-cell response also experienced a longer time without a relapse, (relapse-free survival).
“In patients whose immune system appeared to respond to the vaccine, the recurrence of cancer was delayed compared with patients who did not respond to the vaccine,” O’Reilly says. “That’s the type of early clinical effect we can build on.”
Off-the-shelf KRAS vaccines versus personalized mRNA vaccines?
A different approach to activating immune cells has been led by surgical oncologist Vinod Balachandran, who is investigating whether a personalized mRNA vaccine using proteins from a patient’s pancreatic tumors is safe and immunogenic. In this way, the mRNA vaccine trains the body to protect itself against cancer cells. This vaccine is now being tested in a Phase 2 research study at MSK and other institutions.
Personalized vaccines—while promising—also have challenges: They take time to make and are costly. By contrast, an off-the-shelf vaccine manufactured in batches could be given to patients with minimal delay and would be cheaper to produce. “These findings are exciting because they show we may have more than one way to activate immune cells to target pancreatic cancer,” O’Reilly says.
- This press release was originally published on the Memorial Sloan Kettering Cancer Center website