Peptide Cancer Vaccine Triggered Immune Responses in 70% of Advanced Colorectal Cancer Patients | Research

The takeaway

A pilot trial of CEA and Her2/neu peptide vaccination in 11 advanced colorectal cancer patients was well tolerated and generated immune responses in 70%, with three disease-free patients surviving beyond 10 years.

>10 years survival in 3 patients
Three patients enrolled with no evidence of disease after surgery were alive with no cancer recurrence more than 10 years after peptide vaccination

What the researchers found

Eleven participants with Stage IIIC-IV colorectal cancer received weekly vaccinations with CEA and Her2/neu peptides combined with tetanus helper peptide and GM-CSF in Montanide ISA-51 adjuvant.

Safety: All participants experienced adverse events, with 82% being Grade 1-2 (mild to moderate) — most commonly fatigue and injection site reactions. Two participants (18%) had treatment-related dose-limiting Grade 3 events, both self-limiting.

Immunogenicity: Immune responses (T-cell responses to Her2 or CEA peptides) were detected in 70% of the 10 evaluable participants via interferon-gamma ELISpot assay.

Survival: Median overall survival was 16 months for the full cohort. Remarkably, among three patients enrolled with no evidence of disease, median overall survival was not reached after more than 10 years of follow-up.

Why it matters

Checkpoint blockade immunotherapy works for only a small subset of colorectal cancers (those with microsatellite instability). The vast majority of CRC patients lack effective immunotherapy options. Peptide vaccines that can train the immune system to recognize specific cancer proteins could fill this gap, especially if combined with checkpoint inhibitors. The striking long-term survival in the three disease-free patients is particularly noteworthy and warrants further investigation.

How the study worked

This was a pilot clinical trial (NCT00091286) enrolling HLA-A2+ or HLA-A3+ patients with Stage IIIC-IV colorectal cancer. Participants received weekly subcutaneous vaccinations for 3 weeks with CEA and Her2/neu peptides, tetanus helper peptide, and GM-CSF emulsified in Montanide ISA-51 adjuvant. Adverse events were recorded per NCI CTCAE v3. Immunogenicity was assessed by interferon-gamma ELISpot assay on in vitro sensitized peripheral blood mononuclear cells and sentinel immunized node lymphocytes. Survival was tracked with long-term follow-up.

What this study cannot tell us

This is a very small pilot trial (11 patients, 10 evaluable) without a control group, making it impossible to attribute survival outcomes to the vaccine. The 10-year survival in three patients is intriguing but could reflect favorable disease biology rather than vaccine effect. One participant was retrospectively found ineligible. The study was designed to assess safety and immunogenicity, not efficacy. HLA restriction (A2+ or A3+) limits the eligible patient population. The vaccine did not demonstrate tumor responses in patients with measurable disease.

How to read the evidence

This is a small pilot clinical trial (n=11) without a control group or randomization. It demonstrates safety and immunogenicity but cannot prove clinical efficacy. The long-term survival observations are hypothesis-generating rather than conclusive. Evidence level is early-phase clinical.

When this study was published

Published in 2022 but based on a trial initiated much earlier (NCT00091286), with more than 10 years of follow-up data. The combination of mature survival data with current interest in cancer vaccine-immunotherapy combinations makes this study timely.

The bigger picture

Cancer peptide vaccines have had a challenging history — promising immune responses often fail to translate into tumor shrinkage. However, the field is being revitalized by combining vaccines with checkpoint inhibitors, which remove the 'brakes' that tumors place on the immune system. This trial's demonstration of immunogenicity, along with the remarkable long-term survival in disease-free patients, supports the rationale for testing peptide vaccines as combination partners with approved immunotherapies in colorectal cancer.

Questions still open

Would combining this peptide vaccine with checkpoint inhibitors produce clinical responses in CRC patients who don't respond to checkpoint therapy alone?
What is the clinical significance of the 70% immune response rate — does the strength of the immune response correlate with survival?
Could the long-term survival in disease-free patients be due to the vaccine maintaining immune surveillance that prevented recurrence?

Common questions

How does a peptide cancer vaccine work?

A peptide cancer vaccine contains small pieces of proteins (peptides) that are commonly found on cancer cells but not on normal cells. When injected with an immune-boosting adjuvant, these peptides train the immune system's T-cells to recognize and attack cells displaying those proteins. In this trial, the peptides came from CEA and Her2/neu — two proteins found on many colorectal cancer cells. The goal is to create a targeted immune response against the cancer.

Why did some patients survive more than 10 years while others didn't?

The three long-term survivors had one key advantage: they were enrolled with no evidence of disease (their tumors had already been surgically removed). The vaccine may have helped maintain immune surveillance that prevented cancer recurrence, though this cannot be proven without a control group. Patients who still had detectable cancer at enrollment had poorer outcomes, which is typical in cancer — it is generally easier for the immune system to prevent recurrence of small amounts of residual disease than to shrink large established tumors.

Read the original research

A pilot trial of vaccination with Carcinoembryonic antigen and Her2/neu peptides in advanced colorectal cancer.

International journal of cancer, 150(1), 164-173

View on PubMed ↗Publisher’s paper ↗

Citation

Lynch, Kevin T; Squeo, Gabriella C; Kane, William J; Meneveau, Max O; Petroni, Gina; Olson, Walter C; Chianese-Bullock, Kimberly A; Slingluff, Craig L; Foley, Eugene F; Friel, Charles M. (2022). A pilot trial of vaccination with Carcinoembryonic antigen and Her2/neu peptides in advanced colorectal cancer.. International journal of cancer, 150(1), 164-173. https://doi.org/10.1002/ijc.33793