Vaccine shows promise in preventing recurrence

A vaccine against recurring bowel and pancreatic cancer has shown promise in trials in the US, according to a new study.

Pancreatic and bowel cancers are susceptible to gene mutations called KRAS mutations. These mutations cause cells to grow and divide rapidly, leading to frequent cancer recurrence in patients.

Cancers caused by KRAS mutations are historically difficult to treat and require personalised treatments. The new off-the-shelf vaccine, known as ELI-002 2P, targets these KRAS mutations by activating an immune response in the lymph nodes, which reduces the likelihood of a recurrence.

Following up from data from the AMPLIFY-201 phase 1 trial (February 2024), the vaccine was tested on 25 patients, 20 of whom had recently been treated for pancreatic cancer and five for bowel cancer. These patients had shown minimal traces of circulating tumor DNA (ctDNA) or cancer DNA in their blood, placing them at high risk of cancer recurrence.

The vaccine was administered to the participants before any relapse was detected by traditional radiographic scans, allowing researchers to determine whether it could elicit an immune response.

After a follow-up of almost 20 months, the results, published in the journal Nature Medicine, revealed that the majority of patients generated T-cells specific to fighting the KRAS mutations. This developed immune response reduced those patients’ risk of cancer relapse – thereby improving overall survival rates – and delayed the time before relapse occurred.

Of the patients who had the strongest immune response, a majority of those were cancer free at the 20-month follow-up. The average relapse-free survival for participants was 16.33 months, and the average overall survival was almost 29 months. This time frame is much longer than previous historical expectations.

Researchers also found that almost one in four participants demonstrated a complete clearing of all tumor-related biomarkers, and 67 per cent had developed immune responses to other tumor-related (non-KRAS) mutations as a result of the vaccine.

The study, which is being sponsored and designed by Boston-based biotech Elicio Therapeutics, is still in its early stages. Nonetheless, experts are optimistic about the results, especially considering that KRAS-driven cancers have traditionally been difficult to treat.

The ELI-002 2P vaccine offers a promising approach for generating immune responses aimed at targeting and killing cancer cells. So far, immunotherapy has not been very effective for treating pancreatic cancer, and has been effective in treating only a small number of patients with advanced bowel cancer.

Its off-the-shelf nature – meaning it is standardised and mass-produced – makes it less complex and more affordable than personalised vaccines and therefore more readily accessible for patients.

Bowel cancer is the third most common type of cancer globally and the second most common cause of cancer-related death.

“The importance of developing novel approaches for KRAS-driven cancers cannot be overstated as KRAS mutations are prevalent in several solid tumors,” said Usman Shah, the medical director of gastrointestinal oncology at Atlantic Health’s Overlook Medical Center Summit in New Jersey.

“ELI-002’s ability to induce strong and durable immune responses offers a potential strategy to prevent cancer recurrence in high-risk patients,” added Shah, who was not directly involved in the research.

More research is needed to explore the potential of ELI-002 2P not only to prevent cancer recurrence but also to prevent cancer in individuals who are at high risk. A randomised phase 2 study is currently under way, with the findings so far supporting continued investigation of lymph node-targeted immunotherapy for tumors.