Johns Hopkins-Developed KRAS Vaccine Shows Durable Immune Response in Pancreatic Cancer Prevention Trial

Researchers at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins have published phase 1 results in Cancer Discovery for mKRAS-VAX, an off-the-shelf synthetic long peptide vaccine targeting the six most common KRAS mutations found in pancreatic ductal adenocarcinoma (PDAC).¹ The trial vaccinated 20 individuals at high risk of PDAC due to hereditary predisposition and radiographic evidence of a pancreatic lesion, and found the vaccine stimulated mutant-KRAS-specific effector and central memory T-cell responses in 90% of participants, responses that remained detectable in the blood for up to two years after vaccination.¹ ²

After a median follow-up of 16.5 months, none of the vaccinated individuals developed pancreatic cancer.¹ ² As an exploratory endpoint, the researchers also tracked changes in cyst size and found a higher rate of cyst reduction or resolution among vaccinated individuals (37.5%) compared with an unvaccinated cohort of similar characteristics (6.8%).¹ ²

Neeha Zaidi, MD, associate professor of oncology at the Sidney Kimmel Comprehensive Cancer Center, said in a press release: "This long-lasting response is particularly noteworthy when assessing for possible interception of cancer, which requires long-lasting immunity. In addition, the vaccine was safe and well tolerated, supporting its use in larger cancer interception studies."²

Why focus on cancer interception rather than treatment?

PDAC is typically diagnosed at advanced stages and carries a low five-year survival rate, and roughly 10% of cases stem from hereditary predisposition tied to specific cancer susceptibility genes.² Individuals at high risk due to that predisposition, or due to a concerning pancreatic lesion found on imaging, are usually placed under surveillance, and if a lesion progresses, the current standard of care is surgical resection, a procedure with a recurrence rate of up to 80%.² Compounding the problem, many precursor lesions are microscopic and undetectable by imaging altogether.² mKRAS-VAX is designed to intercept the disease earlier in that progression, aiming to prevent transformation to invasive cancer rather than treating it after diagnosis.¹

Elizabeth Jaffee, MD, deputy director of the Sidney Kimmel Comprehensive Cancer Center, said, "Prevention and interception save lives and reduce the morbidity associated with cancer development and progression. This is especially important for cancers whose early-onset frequency is increasing and for which we do not have effective methods for early detection."²

How does mKRAS-VAX compare to other KRAS-targeted vaccine approaches?

KRAS mutations drive more than 90% of PDAC cases, making the gene a longstanding target for cancer vaccine development across multiple platforms.³ mKRAS-VAX uses a synthetic long peptide format targeting six common KRAS mutations directly, administered via a prime-boost subcutaneous injection schedule.¹ ² That approach differs from Elicio Therapeutics' ELI-002, a competing lymph node-targeted amphiphile vaccine that pairs modified KRAS peptides with a CpG oligonucleotide adjuvant to enhance lymph node delivery.³ In a phase 1 trial of ELI-002 in patients with minimal residual KRAS-mutated disease after standard treatment, relapse-free survival was significantly longer in patients whose T-cell response exceeded a defined threshold, reinforcing the broader principle that durable, robust T-cell responses to KRAS vaccination may correlate with meaningful clinical outcomes, a principle mKRAS-VAX's own two-year immune response durability data also supports.³

What are the trial's limitations?

The study's authors were direct about its constraints: the trial was small and was not designed to assess clinical efficacy of the vaccine.¹ ² Immune analysis was limited to peripheral blood, so it remains unknown whether vaccine-induced T cells actually infiltrate precancerous pancreatic tissue itself.¹ ² Michael G. Goggins, MD, professor of pathology, medicine, and oncology at Johns Hopkins, said, "We observed evidence of stability or regression of the pancreatic cysts in association with the induction and durability of KRAS-specific T-cell responses. However, larger studies are needed to demonstrate that this effect was in fact due to the vaccine."²

What happens next?

A currently enrolling follow-up trial will assess whether vaccine-induced T cells are capable of infiltrating precancer tissue directly, rather than being detectable only in the blood.² Zaidi described the study as representing "the first proof of concept for the use of vaccines for interception of pancreatic cancer in human patients."² Adventris Pharmaceuticals, a company co-founded by both Zaidi and Jaffee, has licensed the mKRAS-VAX technology from Johns Hopkins University and will likely play a role in advancing the vaccine into the larger, cognitively-designed interception studies the researchers say are needed next.¹ ²

References

1. Haldar SD, Huff AL, Wang HH, et al. (2026 Jul 16). First-in-human Testing of a Mutant KRAS Vaccine for Pancreatic Cancer Interception in High-risk Cohorts. Cancer Discovery. https://pubmed.ncbi.nlm.nih.gov/42458705/
2. A Vaccine to Prevent Pancreatic Cancer in High-Risk Individuals Was Safe and Elicited Durable Immune Responses. (2026 Jul 16). EurekAlert!. https://www.eurekalert.org/news-releases/1135900
3. Pant S, et al. (2024 Feb). Lymph-node-targeted, mKRAS-specific amphiphile vaccine in pancreatic and colorectal cancer: the phase 1 AMPLIFY-201 trial. Nature Medicine. https://pubmed.ncbi.nlm.nih.gov/38195752/