Pancreatic Cancer Vaccine Shows Promise in First Human Trial
Researchers at Johns Hopkins School of Medicine have reported promising results from the first human trial of a vaccine designed to prevent pancreatic cancer in high-risk individuals. The experimental vaccine, called mKRAS-VAX, safely generated durable immune responses in 90% of participants, according to a study published July 16 in Cancer Discovery, a journal of the American Association for Cancer Research.
A Vaccine for Cancer Interception
The phase 1 trial enrolled 20 individuals at elevated risk for pancreatic ductal adenocarcinoma (PDAC) due to hereditary predisposition and radiographic evidence of pancreatic lesions, typically small cysts. None had been diagnosed with cancer. The study represents the first proof-of-concept for using vaccines to intercept pancreatic cancer before it develops, an approach known as “cancer interception.”
“Overall, this study represents the first proof of concept for the use of vaccines for interception of pancreatic cancer in human patients,” said Dr. Neeha Zaidi, associate professor of oncology at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, as reported by Fox News.
How the Vaccine Works
mKRAS-VAX is an off-the-shelf synthetic long peptide vaccine targeting the six most common mutations of the KRAS gene, which drives more than 90% of pancreatic cancers. Participants received four subcutaneous injections — priming doses at weeks 1, 3, and 5, followed by a booster at week 13.
The vaccine was well tolerated, with side effects limited to injection-site reactions and temporary flu-like symptoms. No severe toxicity was reported.
Strong Immune Response
Eighteen of the 20 participants (90%) generated mutant-KRAS-specific effector and central memory T cells. Average immune activity increased approximately 18-fold, and half of participants responded to all six KRAS mutations included in the vaccine. The immune responses remained detectable for up to two years, suggesting the potential for long-lasting protection.
Dr. Zaidi noted that “the long-lasting response of this vaccine is particularly noteworthy when assessing for possible interception of cancer, which requires long-lasting immunity.”
Encouraging Early Signals
While the phase 1 trial was designed primarily to evaluate safety and immunogenicity — not clinical efficacy — the exploratory results were striking. After a median follow-up of 16.5 months, no participants developed pancreatic cancer. Among vaccinated individuals, 37.5% experienced shrinkage or disappearance of pancreatic cysts, compared to just 6.8% in an unvaccinated cohort of similar risk.
Dr. Michael G. Goggins, professor of pathology and oncology at Johns Hopkins, cautioned that “larger studies are needed to demonstrate that this effect was in fact due to the vaccine,” according to the AACR news release.
Why This Matters
Pancreatic cancer is one of the deadliest cancers, with a five-year survival rate below 10%, largely because it is typically diagnosed at an advanced stage. KRAS mutations drive more than 90% of PDAC cases, yet the protein was long considered “undruggable” due to its smooth structure.
“Prevention and interception save lives and reduce the morbidity associated with cancer development and progression,” said Dr. Elizabeth Jaffee, deputy director of the Sidney Kimmel Comprehensive Cancer Center and senior author of the study. She emphasized that this is “especially important for cancers whose early-onset frequency is increasing and for which we do not have effective methods for early detection.”
What’s Next
The researchers emphasize that larger phase 2 and 3 trials are needed to confirm clinical efficacy. An ongoing study is investigating whether vaccine-elicited T cells actually infiltrate precancerous tissue. If confirmed in larger trials, KRAS-based vaccination could become a noninvasive preventive tool for high-risk individuals under surveillance for pancreatic cancer.
Dr. Jaffee added that “more studies are needed to find the best vaccine approaches, the best targets and the ideal timing for vaccination,” while also highlighting the need for increased funding to support cancer prevention strategies in high-risk populations.
The study was published in Cancer Discovery with the DOI 10.1158/2159-8290.CD-25-2245 and is registered on ClinicalTrials.gov under identifier NCT05013216.