A new experimental vaccine is showing promise in preventing difficult-to-treat pancreatic and colorectal cancers from returning after patients have received standard treatments, such as chemotherapy and surgery, to try to eliminate the disease.

This new strategy targets mutations in the KRAS gene, which are present in 20 to 25% of human tumors, including nearly 90% of those in pancreatic cancers and 40% of colorectal cancers.

Researchers have long been able to detect these mutations. Still, until recently, they were considered impossible to target with drugs or immunotherapies, so for years the challenge had been getting the immune system to react against them.

Now, a group of researchers from the Massachusetts Institute of Technology (MIT) has tested in humans a vaccine that could forever change this story. 

In a Phase 1 clinical trial, the researchers have demonstrated that it is effective in training the immune system to detect and attack the mutations, and that, so far, it does not present any life threatening risks or side effects.

The study, published in Nature Medicine, included 25 people—20 with pancreatic cancer and five with colorectal cancer—who had already completed treatment but still had traces of the disease that can be detected with blood tests. All of these people also had a high risk of relapse.

Cancer Vaccine: a Direct Trip to the Lymph Nodes

The vaccine, called ELI-002 2P, contains two laboratory made peptides—small molecules—that mimic KRAS mutations. It is not the only vaccine to use this strategy, but it is the first to target the immune system for training successfully. 

Usually, when tumor peptides are injected, they stay at the injection site and degrade rapidly, so the researchers devised a way to create a transport mechanism that stops only when it reaches the lymph nodes. 

These are small, bean-shaped structures that are part of the immune system, acting as filters that trap and destroy foreign substances, such as bacteria, viruses, and cancer cells.

Inside these nodes are T cells, a type of white blood cell that is capable of recognizing and destroying these threats.

To train the immune system to recognize KRAS mutations, the vaccine includes the peptides and an immune system stimulant attached to a lipid—or fatty—tail that sticks to albumin.

Albumin is a naturally occurring protein present in human blood that can transport substances to lymph nodes. Thus, the vaccine passes itself off as a regular “cargo” and travels directly to these sites, rather than getting stuck in the muscle or skin.

A Sustained Immune Response Against KRAS Mutations

In the study, researchers report that approximately 85% of treated participants had an immune response against KRAS mutations. Of these, 24% showed complete remission after a 20-month follow-up.

Furthermore, in nearly 70% of patients, the vaccine triggered a phenomenon called antigen spreading, where the immune system, once activated, began to recognize other tumor cells that were not present in the vaccine.

This is encouraging, since in the case of pancreatic cancer, the risk of recurrence is estimated to be very high—60 to 80% of cases in less than five years.

So, although this vaccine does not prevent the onset of cancer, it can prevent it from returning. 

However, the authors caution that its true efficacy can only be verified in larger trials that include control groups that do not receive the vaccine. 

Looking ahead, they are already planning a phase two clinical trial that includes peptides targeting a broader range of KRAS mutations. 

In the meantime, it’s exciting to know that their strategy appears to be able to give our immune system a clear message that those are the cells it needs to find and destroy.