Imagine being told that you carry a genetic mutation that significantly increases your risk of developing cancer.
For many people with Lynch syndrome, that is their reality. They may spend decades undergoing regular colonoscopies and other forms of surveillance, knowing that cancer could still develop.
But what if a vaccine could change that?
The idea of vaccinating someone against cancer once sounded more like science fiction, but it is increasingly becoming a reality.
Vaccines train our immune system to recognize something as a threat and prepare our bodies to respond. Cancer vaccines apply this principle to cancer cells. Therapeutic cancer vaccines aim to help the immune system recognize and attack cancer that has already developed, or microscopic cancer cells remaining after treatment. Preventive cancer vaccines, such as the human papillomavirus (HPV) vaccine, protect against viral infections that can later develop into cancer.
Newer vaccines attempt something different. They aim to teach our immune system to recognize abnormalities produced by cancer or precancerous cells themselves.
This could have major implications for colorectal cancer. In 2026 alone, an estimated 25,300 Canadians will be diagnosed with colorectal cancer and 9,200 will die from it.
For some, however, their risk begins long before a tumour appears.
Lynch syndrome is one of the most common inherited cancer syndromes, affecting approximately one in 300 people. It results from mutations affecting the DNA mismatch repair system, essentially the machinery cells use to correct mistakes when DNA is copied. When that system does not work properly, mutations accumulate and the risk of cancers, particularly colorectal and endometrial cancers, increases significantly.
Currently, much of Lynch syndrome management focuses on preventing cancer or finding it early. For colorectal cancer, this means frequent colonoscopies beginning at a younger age than for the general population. While colonoscopy provides effective surveillance, it is not perfect; Lynch-associated cancers can sometimes develop between examinations. There is also evidence that daily aspirin can reduce colorectal cancer risk in people with Lynch syndrome. Still, neither surveillance nor aspirin eliminate the underlying risk.
The biology of Lynch syndrome makes it a particularly interesting target for vaccine development. As abnormal cells accumulate mutations, they can produce proteins, known as neoantigens, that are different from those found in normal cells. Some of these abnormalities appear repeatedly across people with Lynch syndrome, creating the possibility of teaching the immune system to recognize them before cancer becomes established.
The idea is not to eliminate Lynch syndrome itself. Someone who inherits the mutation would still carry it. Instead, the hope is that vaccination could teach their immune system to recognize abnormal cells that develop before those cells have the opportunity to become cancerous.
And this is no longer purely theoretical.
One vaccine, Nous-209, is designed to target shared abnormal proteins associated with mismatch repair-deficient cancers. Early results published in Nature Medicine are encouraging. In a phase 1b/2 trial involving 45 people with Lynch syndrome, all 37 participants who could be evaluated for immune response developed a response to the vaccine, with most maintaining detectable responses one year later. No serious adverse events related to the vaccine were reported.
These results, while promising, do not mean we have a vaccine that prevents colorectal cancer. The study was small and primarily designed to determine whether the vaccine was safe and capable of generating an immune response. Larger studies will need to determine whether that translates into fewer precancerous lesions and, ultimately, fewer cancers.
Another approach is taking advantage of a technology that has become much more familiar over the past several years: mRNA.
Researchers at the University of Oxford and Moderna have begun studying mRNA-4194, an investigational vaccine designed to prevent Lynch-associated cancers. The INTERCEPT-Lynch trial will initially examine the vaccine’s safety and its ability to produce an immune response.
The concept is fascinating. Instead of waiting for someone with Lynch syndrome to develop cancer and then treating it, could we train their immune system to intervene earlier?
Developments in therapeutic cancer vaccines also are part of the story. A vaccine targeting common KRAS mutations shared by groups of patients has shown encouraging early results in patients with pancreatic and colorectal cancers. The vaccine is “off-the-shelf,” meaning it can be mass produced. Meanwhile, an mRNA vaccine for pancreatic and colorectal cancers that is custom made for each patient is in a Phase 2 clinical trial.
Since both vaccines are intended to be given after surgery, this raises the possibility that cancer vaccines could become an important adjunct to colorectal cancer surgery.
Curative-intent colorectal cancer surgery aims to remove the visible tumour and its regional lymphatic drainage. However, even after a seemingly successful surgery, microscopic cancer cells can remain elsewhere in the body and eventually lead to recurrence, sometimes requiring further treatment such as chemotherapy or radiation. But what if surgery could remove the cancer we can see while a vaccine helped the immune system target what we cannot?
The post-operative period could therefore be a particularly important setting for vaccination. As Professor Robert Jones discussed on Behind the Knife, rather than asking the immune system to fight a large, established tumour, vaccination may be particularly useful after visible disease has been removed and any remaining cancer is microscopic.
Moreover, circulating tumour DNA, or ctDNA, could take this concept even further. ctDNA testing looks for fragments of tumour DNA circulating in the blood after treatment and may help identify patients at particularly high risk of recurrence. This raises the possibility of using a blood test to help determine who might benefit most from additional treatment, including future cancer vaccines.
The BNT122-01 trial explored one version of this approach, testing an individualized cancer vaccine in patients with ctDNA detected after surgery for stage II or III colorectal cancer. The trial was stopped early in 2026 after the vaccine did not show sufficient evidence of benefit to justify continuing the study. While this was a setback for this particular vaccine strategy, it also highlights how early the science of cancer vaccines remains. Meanwhile, ctDNA itself continues to show promise as a way to identify patients at increased risk of recurrence after surgery and could eventually help determine who might benefit most from additional treatment.
This could eventually create a very different cancer-care pathway: surgery removes what we can see, blood testing helps identify what may remain and vaccination teaches the immune system what to look for next.
However, there are still many questions to answer.
If a Lynch syndrome vaccine reduces cancer risk, would patients still need colonoscopies as frequently? How long would protection last? Would boosters be required? For patients who have already developed colorectal cancer, would vaccines replace chemotherapy for some patients or be added to it? Could they work better alongside immunotherapy? Could vaccines enhance response to other treatments, such as immunotherapy or neoadjuvant chemotherapy and radiation for rectal cancer, allowing more patients to achieve a complete clinical response and safely avoid surgery? And could ctDNA help determine who receives them?
Cost also cannot be ignored. Personalized vaccines may require tumour sequencing, sophisticated computer analysis and manufacturing an individualized product for a single patient. Even if the science works, integrating this technology into a publicly funded health-care system could be expensive.
Even if we can answer all the questions and cover the costs, there is still another important issue: before we can vaccinate people with Lynch syndrome, we first need to know who has it.
In Ontario, for example, tumour testing for abnormalities in the mismatch repair system can help identify patients with colorectal cancer who may have Lynch syndrome, with further genetic testing used to establish an inherited diagnosis. But identifying people only after they develop cancer misses the very population a preventive vaccine would hope to reach. A successful vaccination strategy would therefore require broader and more consistent access across Canada to genetic assessment, counselling and cascade testing, in which relatives of someone with Lynch syndrome are offered testing themselves.
A breakthrough in cancer prevention will have limited impact if many of the people who could benefit remain unidentified.
These challenges do not take away from the potential of cancer vaccines. They highlight how much work remains before an exciting scientific discovery becomes part of routine cancer care. Producing an immune response is not the same as preventing cancer. Most of these vaccines remain experimental, and years of research will be needed to determine whether they reduce cancer diagnoses, recurrence and death.
Still, it is difficult not to be hopeful about where this field is heading.
The goal may no longer be to find cancer earlier or treat it better once it appears.
One day, for some patients, it may be to stop it from appearing at all.
