A pioneering cancer vaccine designed to target a common genetic mutation has shown early promise in preventing the return of aggressive pancreatic cancers, according to results from a small clinical trial.
Pancreatic cancer remains one of the deadliest malignancies, with a five-year survival rate of just 13%, data from the American Cancer Society show. Even after treatment, up to 80% of cases recur, according to the National Institutes of Health.
“This is the disease that most urgently needs a way to stop recurrences,” said Dr. Zev Wainberg, co-director of the gastrointestinal oncology program at the University of California, Los Angeles, and a lead investigator in the trial.
The vaccine, ELI-002 2P, targets mutations in the KRAS gene — alterations found in approximately 25% of all cancers, including up to 90% of pancreatic cancers and around 40% of colon cancers, the University of Texas MD Anderson Cancer Center reports. Historically considered “undruggable,” KRAS mutations are now becoming more accessible to targeted treatments through new scientific approaches.
ELI-002 2P works by using synthetic peptides — short chains of amino acids — to train the immune system to identify and destroy cancer cells carrying KRAS mutations. Unlike many personalized cancer vaccines, this one is “off the shelf,” meaning it does not require tumor sequencing before administration.
The Phase 1 trial, published August 12 in Nature Medicine, involved 25 patients — 20 with pancreatic cancer and five with colon cancer — all of whom had KRAS mutations and had undergone surgery and chemotherapy. Blood tests revealed traces of residual disease, cancer cells too small to detect via imaging. Participants received up to six priming doses of the vaccine over six months, with 13 also receiving booster shots.
Key findings included:
- 85% (21 of 25 participants) mounted an immune response to KRAS mutations.
- About two-thirds of those showed a strong enough immune reaction to help eliminate remaining cancer cells.
- Nearly 70% developed immunity to tumor targets not included in the vaccine.
- A subset of “super-responders” had exceptionally strong immune responses and the most favorable outcomes.
- Among pancreatic cancer patients, the average survival was 29 months, with participants remaining cancer-free for more than 15 months on average after vaccination.
“Those results far exceed the typical rates for surgically removable pancreatic cancers,” Wainberg noted.
Experts say the success may be due to the vaccine’s unique peptide design, which features a molecular “tail” that allows the compounds to remain in lymph nodes — where immune cells are activated — for longer periods.
Cancer vaccines have historically been challenging to develop because cancer cells share many proteins with healthy tissue, making safe targets scarce. However, advances in mRNA technology and rapid gene sequencing are opening new possibilities for more effective immunotherapies.
A Phase 2 clinical trial is now underway to compare ELI-002 2P with standard post-surgical treatment.
“The link between T-cell responses and long-term survival is compelling,” said Dr. Stephanie Dougan, associate professor at Dana-Farber Cancer Institute, who was not involved in the research. “The idea that KRAS can be effectively targeted is very exciting.”
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