By Deborah Borfitz 

August 4, 2026 |  A new era of cancer interception has begun, marked by a groundbreaking first-in-human clinical trial of a vaccine targeting mutant KRAS, one of the most common genetic drivers of pancreatic cancer. The strategy was not only found to be safe but to generate durable immune responses in high-risk individuals to fend off cancer onset, according to Neeha Zaidi, M.D., associate professor of oncology at Johns Hopkins and co-senior author of the study. 

The study was proof of concept that mKRAS-VAX, a peptide-based vaccine, could get immune cells activated against its target (Cancer Discovery, DOI:10.1158/2159-8290.CD-25-2245). Participants experienced a median 18.2-fold increase in mutant KRAS-specific T-cell responses, as well as CD4- and CD8-positive T-cell responses and the production of memory T cells. Vaccine-induced mutant KRAS-specific T-cell clones remained detectable for as long as two years after vaccination.  

The beauty of vaccines is that they train the immune system to establish long-term memory cells to fight off disease, and people at risk for cancer need a lifetime of this induced immunity protection, says Zaidi. The vaccine-specific immune response was still detectable up to two years after vaccination in those who had long-term follow-up available, all of whom had a hereditary predisposition to pancreatic cancer and an imaging-identified pancreatic abnormality. The magnitude of immune response decreased over time, suggesting that booster shots may be needed to periodically wake up T cells and reinforce the body’s surveillance. 

Rather than preventing the disease from initiating, interception actively identifies and eliminates pre-cancerous cells or very early molecular changes to reverse or halt the process of cancer formation, Zaidi explains. The idea here is to stop cancer before it is established, after which it knows how to put up all sorts of barriers and signals to protect itself and resist treatments. 

Interception means treating the precancer, which distinguishes it from preventive approaches, such as HPV vaccination that is often given prior to exposure to the virus, says Zaidi. “If it works ... the general impact is very high.”  

Pancreatic cancer is “uniquely suited for interception because we have a singular kind of target to go after,” namely some type of KRAS mutation expressed in up to 90% of all patients, she adds. “It’s one of the initiating mutations that occurs when a precancer [in the pancreas] develops.” The transformation of a precancerous lesion into cancer generally takes a decade, providing a window of opportunity to interrupt the process. 

The latest Johns Hopkins study was the first time the interception approach has been tried in people who don’t yet have an active cancer diagnosis. Researchers here and elsewhere have been developing vaccines for people who already have cancer, including the KRAS-targeted variety, Zaidi says. 

These “off-the-shelf” vaccines are relevant to other cancers because mutated KRAS proteins act as universal flags across multiple tumor types, most notably lung and colorectal cancers but also less common types such as cholangiocarcinoma (bile duct cancer). Personalized vaccines are also under development for cancer patients following surgery in hopes of training the immune system to recognize remaining cancer cells and prevent recurrence. 

Seeking Clues  

The reality currently is that most people are newly diagnosed with pancreatic cancer when it is already at an advanced stage, which is when symptoms first develop, says Zaidi. Because the pancreas is located deep within the abdomen, early tumors can grow without pressing on other organs or causing noticeable signs.  

“Unfortunately, we don’t have anything curative to offer even people with early-stage disease right now,” she says, noting that disease recurrence is also very high even among patients who have had a tumor surgically removed and have received chemotherapy. Identifying people at high risk has therefore become the focus of researchers everywhere.  

The uptick in early-onset cancers has included pancreatic cancers diagnosed before age 50 or 55 (The Lancet Gastroenterology & Hepatology, DOI: 10.1016/S2468-1253(23)00039-0). But even for people identified as being at risk because of a germline or genetic predisposition or intraductal papillary mucinous neoplasms (IPMNs, precancerous pancreatic cysts) seen on imaging, “it’s kind of a watch and wait game,” says Zaidi. Aside from surgery, which carries its own risk, there is nothing that can be done currently to intervene. 

That would make mKRAS-VAX a gamechanger, if it goes well with the vaccine’s development, she notes. For the phase 1 trial, participants received four doses of the vaccine over 13 weeks, which is a common dosing schedule with peptide vaccines. The initial three doses were administered every other week to “rev up” the immune system, followed by a final booster vaccine after eight weeks. 

The trial was prompted by an earlier study with the KRAS vaccine in patients who had undergone surgery and were at high risk of cancer recurrence, which published earlier this year (Nature Communications, DOI: 10.1038/s41467-026-68324-4). In the first phase 1 trial, the vaccine generated a strong immune response in 12 patients who have remained disease-free for at least five years. 

These patients all received the standard of care, which also included chemotherapy, says Zaidi. They then received the vaccine plus immune checkpoint inhibitors.  

Therapeutic Potential 

An additional finding with the 20-patient cohort is that three of the participants experienced complete radiographic resolution of small pancreatic cysts, while three others experienced partial regression and the remaining cysts remained stable. A historical cohort of unvaccinated people did not have cyst resolution, and some had an increase in cyst size. This was of course a retrospective exploratory analysis, says Zaidi, so imaging changes over time will need to be examined further. 

These sorts of interception trials require an innovative design since cancer can take many years to develop, making traditional endpoints like tracking tumor growth or overall survival too slow and impractical, continues Zaidi, in explaining why the study looked for clues in the blood. A subsequent trial now underway is vaccinating participants with IPMNs who are thought to be at very high risk for cancer transformation and are therefore treated surgically. This will enable the research team to examine both the blood and surgery tissue to see if the vaccine-specific T cells are infiltrating into the precancer. 

The most obvious clinical direction for mKRAS-VAX is to vaccinate people having one of the six most common KRAS mutations that the vaccine targets or a known precancerous lesion, she says. “Everyone who gets diagnosed with pancreatic cancer now gets germline testing, so they know if they had an inherited predisposition.” If that’s the case, first-degree relatives will typically be referred for targeted genetic testing and can be referred for surveillance programs if necessary. 

A few other vaccines are now under development to intercept various cancer types in high-risk individuals, she notes. The scale of their impact is potentially huge, as suggested by how much HPV and HBV vaccines have dramatically lowered the incidence of cervical and liver cancer worldwide while being exceptionally safe and highly cost-effective.