DNA-based HER2 vaccine has stronger anti-cancer immune response compared to HER2 peptide vaccines
- Sarah White
- 3 days ago
- 2 min read
At the UW Cancer Vaccine Institute, we are working to develop vaccines that train the immune system to recognize and eliminate cancer. At the 2025 San Antonio Breast Cancer Symposium, we shared new data comparing two of our HER2-targeted therapeutic vaccine platforms for people with advanced HER2-positive breast cancer. About 20% of all breast cancers overexpress the HER2 protein, which can make the disease more aggressive. Our goal is to create vaccines that strengthen the body’s ability to mount a durable immune response against HER2-expressing tumor cells.
Over time, our team has developed several HER2 vaccine approaches. Earlier versions used small fragments of the HER2 protein, known as peptides, which are synthesized in a lab and then administered to patients. These vaccines can stimulate an immune response, but they introduce only a limited amount of HER2 protein. More recently, we have advanced a DNA-based vaccine, known as the HER2 ICD vaccine, that delivers a DNA plasmid encoding segments of HER2. After vaccination, a patient’s own cells temporarily produce these HER2 fragments, potentially exposing the immune system to more antigen over a longer period and generating a stronger, broader response.
To compare these platforms, we analyzed immune responses from two of our clinical trials: a Phase I study of 66 patients who received the HER2 ICD DNA vaccine and a Phase II study of 38 patients who received the HER2 peptide vaccine. All participants had stage III or IV HER2-positive breast cancer and were either without evidence of disease or had stable bone-only disease at the time of vaccination.
In both studies, we measured immune responses to the part of HER2 that was targeted by both vaccines and also looked to see if the immune system showed evidence of recognizing other parts of HER2 not included in the vaccine, a phenomenon called epitope spreading. This broadening of the immune response is associated with stronger, more durable immunity.
Across multiple analyses, the DNA vaccine demonstrated stronger, more consistent, and more comprehensive immune activation. It generated higher T-cell responses, supported more robust epitope spreading, and showed advantages even among individuals who did not respond strongly to the peptide vaccine. Both vaccines were well tolerated overall.
Some patients had evidence of immune responses to HER2 even before being vaccinated as a result of previous treatments. Among patients who did not have HER2-specific immunity at baseline, both vaccines successfully generated strong T-cell immune responses and evidence of epitope spreading. However, only the DNA vaccine increased immune responses in patients who already had some HER2 immunity at the start of the study, while the peptide vaccine did not show a similar increase in this group. Additionally, the DNA vaccine consistently resulted in expanding recognition of additional HER2 regions (epitope spreading) in all patients, while the peptide vaccine only did so in patients without preexisting immunity.
Taken together, our findings show that while both vaccine platforms can stimulate HER2-specific immunity in patients who begin without baseline responses, the DNA vaccine offers a more potent and versatile approach. Its ability to broaden and amplify HER2-specific T-cell immunity—even in patients with preexisting responses—supports its promise as a next-generation platform for therapeutic cancer vaccination.
