Colorectal and pancreatic cancers—the second and third leading causes of cancer death, respectively—often have mutations in the KRAS protein. Now, a new vaccine that targets KRAS has shown encouraging early results as a potential off-the-shelf treatment for patients with pancreatic cancer or colorectal cancer, according to a study co-led by researchers at Memorial Sloan Kettering Cancer Center (MSK).
Some cancer vaccines, such as mRNA-based vaccines, can be personalized and custom-made for each patient. Personalized vaccines—while promising—also have challenges such as cost and long production times. However, a cancer vaccine that could be used as a potential off-the-shelf treatment for certain patients that share specific mutations is an intriguing possibility. The off-the-shelf vaccine could be manufactured in batches and given to patients with minimal delay. It also would be cheaper to produce.
“Having a vaccine that’s ‘off-the-shelf’ would make it easier, faster, and less expensive to treat a larger number of patients,” said Eileen O’Reilly, MD, a gastrointestinal oncologist at MSK. “This gives hope for people with pancreatic and colorectal cancer who have been out of effective treatments when their disease returns.”
The vaccine being tested here, ELI-002 2P, is described to enhance “lymph node delivery and immune response using amphiphile modification of G12D and G12R mutant KRAS (mKRAS) peptides (Amph-Peptides-2P) together with CpG oligonucleotide adjuvant (Amph-CpG-7909).”
The authors noted, in a new paper published in Nature Medicine, that the vaccine was safe and induced considerable T-cell responses in patients with immunotherapy-recalcitrant KRAS-mutated tumors.
The paper reports results from a Phase I trial that involved 25 patients whose pancreatic or colorectal cancer had certain KRAS mutations and were at high risk of the 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. The authors report that 84% of patients had the desired immune response, meaning that immune T cells targeting KRAS-mutated cancer cells were activated and grew in number. Also, in 84% of patients, the amount of tumor DNA circulating in the blood was reduced. In 24% of patients, the tumor DNA was completely absent.
Perhaps most significant, patients who had a higher T-cell response also experienced a longer time without the disease returning, known as 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,” said O’Reilly. “That’s the type of early clinical effect we can build on.”
“These findings are exciting because they show we may have more than one way to activate immune cells to target pancreatic cancer,” she added.