Johns Hopkins phase 1 trial: mKRAS vaccine triggers 90% T-cell response against KRAS
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American researchers reported that an experimental peptide vaccine targeting six common KRAS mutations triggered a T-cell immune response in 90% of high-risk participants in a phase 1 trial. None of the 20 participants with precancerous pancreatic changes developed cancer during a median follow-up of 16.5 months, according to the study published in Cancer Discovery. The vaccine, developed at Johns Hopkins' Sidney Kimmel Comprehensive Cancer Center, also led to cyst reduction or disappearance in 37.5% of patients, even as larger trials are needed to confirm its preventive effect.
Vaccine Design and Trial
The mKRAS-VAX peptide vaccine targets six of the most common KRAS gene mutations, which are present in 90–95% of pancreatic adenocarcinomas. Researchers at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins enrolled 20 individuals with hereditary predisposition to pancreatic cancer and precancerous cysts. The phase 1 trial, published in Cancer Discovery, was designed primarily to assess safety and immune response rather than cancer prevention efficacy.
Immune Response and Safety
After vaccination, 90% of participants developed a T-cell response against the mutant KRAS protein, with immunity detected for up to two years in some. No serious safety issues emerged during the trial, and the vaccine was well tolerated. Over a median follow-up of 16.5 months, none of the 20 participants progressed to pancreatic cancer.
Impact on Cysts
In 37.5% of participants, precancerous pancreatic cysts shrank or disappeared entirely following vaccination. By comparison, among patients with similar precancerous changes who did not receive the vaccine, cyst regression had been observed in only 6.8% of cases, according to the study. Researchers called this signal promising but emphasized that the findings are preliminary and require confirmation in larger cohorts.
What's Next
The Johns Hopkins team plans larger and longer-term trials to determine whether the vaccine can definitively reduce pancreatic cancer risk. It remains unclear whether the robust T-cell response will translate into actual cancer prevention over many years, as pancreatic cancer typically develops slowly.
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Johns Hopkins phase 1 trial: mKRAS vaccine triggers 90% T-cell response against KRAS
