Cancer Vaccines Are Coming for Colorectal Cancer

For a long time, "cancer vaccine" sounded like a contradiction. Vaccines were something you got to stay healthy, to stop a disease before it started. Cancer treatment meant surgery, chemotherapy, radiation. But in the past few years, clinical trials have shown vaccines can also help treat cancer that's already there, by teaching the immune system to recognize and attack cancer cells the way it fights off a virus.

Colorectal cancer (CRC) is one of the diseases where this idea is furthest along. Researchers are testing two very different kinds of cancer vaccines: one made in advance and used for many patients at once, and one custom-built for a single patient from their own tumor. Both aim to do the same job after surgery or during treatment: train T-cells to find and destroy any cancer cells left behind, so the disease has a harder time coming back.

Two Ways to Train the Immune System

A cancer vaccine works by showing the immune system a small piece of a cancer cell, usually a fragment of a protein that's abnormal in a way healthy cells aren't. Once immune cells learn to recognize that fragment as foreign, they can hunt down any cell that carries it.

The first approach, "off-the-shelf," targets a mutation that shows up again and again in many patients' tumors. Because the target is shared, one vaccine can be manufactured ahead of time and used for anyone whose cancer carries that mutation.

The second approach, personalized or "neoantigen" vaccines, starts fresh with each patient. Doctors sample a person's own tumor, find the mutations unique to it, and build a vaccine, often using mRNA, around those exact mutations. No two patients get the same vaccine.

Off-the-Shelf: One Vaccine, Many Patients

One example is ELI-002, which targets KRAS, one of the most common cancer-driving mutations in solid tumors. Roughly 90% of pancreatic cancers and about half of colorectal cancers carry a KRAS mutation, which is why one vaccine can help so many people.

ELI-002 doesn't need a sample of anyone's tumor to be made. It's built from lab-made protein fragments that travel to nearby lymph nodes, where they teach T-cells to recognize KRAS-mutated cells. In a completed early trial, 25 patients with pancreatic or colorectal cancer received the vaccine after surgery, while small traces of cancer still remained in their bodies. After nearly two years of follow-up, 84% developed an immune response to KRAS, and for many, that response lasted. In about one in four patients, all detectable traces of the cancer's genetic signature disappeared from their blood.

The stronger the immune response, the better patients tended to do. Patients with a strong response were, on average, still cancer-free when the study ended. Those with a weaker response relapsed after about 3 months and lived a median of about 16 months. A newer version targeting even more KRAS mutations has already finished enrolling patients for a larger follow-up study.

A second off-the-shelf vaccine, NOUS-209, targets Lynch syndrome, an inherited condition that affects about 1 in 300 people and raises their lifetime risk of colorectal and some other cancers as high as 80%. People with Lynch syndrome inherit a glitch in the genes that normally fix DNA errors, so their tumors build up the same repeating mutations over and over. Because those mutations show up again and again, both across different patients and in a single patient's tumors over time, they're a good target for a vaccine that can be made in advance rather than built fresh for each person. NOUS-209 trains the immune system to recognize 209 of these repeat mutations at once.

In a trial of 45 people with Lynch syndrome, the vaccine was well tolerated, with no serious side effects tied to treatment; the most common were mild soreness where the shot was given and tiredness. Everyone who could be tested developed a measurable immune reaction to the targeted mutations, and that response was still detectable a year later in 85% of participants. A separate genetic study confirmed these same mutations show up consistently in Lynch syndrome tumors, including new tumors that develop later in the same patients, which suggests NOUS-209 could eventually help prevent new Lynch syndrome associated cancers before they even start, an approach researchers call cancer interception.

Personalized mRNA Vaccines: Built From One Patient's Tumor

This approach has shown real activity in colorectal cancer, including in patients who usually respond poorly to immunotherapy. Most advanced colorectal cancers are "microsatellite stable" (MSS), meaning they lack the DNA repair problems that make some cancers highly responsive to immune-boosting drugs. MSS tumors make up the large majority of advanced CRC cases and have historically gotten little benefit from immunotherapy alone.

mRNA is what makes this kind of fast, individualized vaccine possible in the first place. Instead of manufacturing a protein in a lab, an mRNA vaccine hands a patient's own cells a short set of instructions and lets those cells build the target protein themselves. It's the same basic technology used in the COVID-19 vaccines, and it happens to be a good fit for cancer vaccines because a new sequence can be designed and produced in weeks rather than months once a patient's tumor mutations are known.

One personalized vaccine, GRANITE, was tested in a randomized trial of patients with newly diagnosed metastatic MSS colorectal cancer, alongside standard immune-boosting medication. Early results showed the vaccine lowered the risk of the cancer getting worse or patients dying by about 21%, rising to a 38% risk reduction in patients who had less cancer in their body at the start of treatment. Side effects were mild, and no one had to stop treatment because of them.

A smaller study out of Wenzhou Medical University in China told a similar story on a much smaller scale. Researchers built personalized vaccines for six patients with MSS colorectal cancer whose disease had come back or spread after surgery and chemotherapy. Four of the six developed a measurable immune response, and those four went nearly twice as long without their cancer progressing as the two who didn't respond (19 months versus 11 months). One patient's liver metastases visibly shrank on scans after starting the vaccine. The study was very small, but it adds to growing evidence that even hard-to-treat MSS tumors can be pushed into an immune response with the right approach.

Another cancer vaccine candidate called autogene cevumeran is being tested in colorectal cancer patients who've had surgery to remove their tumor and completed chemotherapy but still have trace amounts of cancer DNA (ctDNA) in their blood, a sign the disease could return. In that trial, patients receive the vaccine instead of simply being watched for recurrence, which is the current standard approach. So far, the vaccine has reliably triggered a strong, tumor-specific immune response in patients who received it. Whether that immune response will translate into fewer recurrences is still an open question, and the study is ongoing.

Why Timing Matters

Both vaccine types point to the same ideal moment for treatment: shortly after surgery, while remaining cancer is at its lowest and hasn't had time to build up defenses against the immune system. Researchers call this the perioperative window, the stretch of time around surgery when a tumor sample can be analyzed, a vaccine built or ordered, and treatment started before any leftover cancer cells regrow. For personalized vaccines especially, this is a race against the clock: the sample has to stay in good condition, and the vaccine has to be ready while that early window is still open.

What Comes Next

Neither vaccine type is finished being studied. GRANITE is continuing toward a larger trial and eventual conversations with regulators, and results from the newest ELI-002 are still being analyzed. But the trend is encouraging: both mass-produced and custom-built cancer vaccines are giving doctors a genuinely new way to fight colorectal cancer, including the MSS tumors that standard immunotherapy has struggled to touch on its own. For a disease where recurrence after surgery remains one of the biggest risks patients face, that's a meaningful step forward.

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