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by Dr. C.H. Weaver M.D. 11/2022

DNA Vaccine for HER2 + Breast Cancer

An experimental vaccine against breast cancer has been reported to safely generate a strong immune response according to researchers from the University of Washington School of Medicine. The phase I clinical trial was designed to evaluate the safety of a vaccine that targets a protein called human epidermal growth factor receptor 2 (HER2) and to see if it generated an immune response to the protein.1

The DNA vaccine is different than previous protein vaccines which typically contain a protein or part of a protein that you want the immune system to target. DNA vaccines contain the DNA instructions for the target protein and when injected the DNA is taken up by cells at the injection site, which then start to produce the protein encoded in the vaccine’s DNA instructions. 

In the trial 66 women with metastatic breast cancer received one of three vaccine doses being evaluated. The women were then followed for three to 13 years - researchers wanted to ensure the vaccination did not, over time, trigger an autoimmune response against other healthy tissues expressing HER2.

The vaccine was found to be safe and successfully stimulated the desired cytotoxic immune response without triggering severe side effects. Although the study was not designed to see if the vaccine could slow or prevent progression of the cancer 80% of the women are alive which is better than would be expected in patients with similar stages of breast cancer, about half of whom would be expected to die within 5 years of treatment.1

This is not the first vaccine developed to target the HER2 protein.  The HER2 protein, also known as human epidermal growth factor receptor 2, is found on the surface of certain cancer cells, including breast cancer. In normal cells HER2 helps control cell growth. Cancer cells, however, can make too much of the protein, which can cause cells to grow more quickly and be more likely to spread to other parts of the body.2-5

Doctors at Moffitt Cancer Center in Tampa Florida are also working on a vaccine that would help early-stage breast cancer patients who have HER2 positive disease.

The researcher team developed a vaccine that helps the immune system recognize the HER2 protein on breast cancer cells. Their approach involves creating the vaccine from immune cells called dendritic cells that are harvested from each individual patient and then used to create a personalized vaccine.

In order to determine if the HER2-dendritic cell vaccine is safe and effective, the Moffitt researchers performed a clinical trial that included 54 women who have HER2-expressing early-stage breast cancer. The dendritic cell vaccines were prepared by isolating dendritic cells from each patients’ blood and exposing them to fragments of the HER2 protein. Patients were injected with a dose of their personal dendritic cell vaccine once a week for 6 weeks into either a lymph node, the breast tumor, or into both sites.

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The results also showed the vaccine was able to stimulate an immune response in the majority of the patients. Approximately 80% of trial participants had a detectable immune response in their peripheral blood and/or in their sentinel lymph node wherein their cancer is most likely to spread.5

Moffitt researchers assessed the effectiveness of the vaccine by determining the percentage of patients who had detectable disease within surgical specimens after resection. The absence of disease is termed a pathological complete response. They report that 13 patients achieved a pathological complete response and patients who had early non-invasive disease called ductal carcinoma in situ (DCIS) achieved a higher rate of pathological complete response than patients who had early-stage invasive disease. Additionally, patients who achieved a pathological complete response had a higher immune response within their local sentinel lymph nodes.

“These results suggest that vaccines are more effective in DCIS, thereby warranting further evaluation in DCIS or other minimal disease settings, and the local regional sentinel lymph node may serve as a more meaningful immunologic endpoint,” said Czerniecki, chair of the Department of Breast Oncology at Moffitt.

GP2 HER2 Derived Vaccine

The HER2-derived vaccine, known as GP2, is designed to provoke the body’s immune system to fight cancer by recognizing tumor cells that express HER2. It is administered in addition to standard breast cancer treatment, such as Hercpetin® (trastuzumab), with the goal of preventing recurrence.

To measure how effectively the GP2 vaccine might help prevent recurrence in women with HER2-postive breast cancer, researchers evaluated patients who were disease free after treatment with Hercpetin. A portion of participants (89) was randomly selected to receive the GP2 vaccine plus granulocyte-macrophage colony-stimulating factor (GM-CSF), an immunotherapy to stimulate an immune response, and another 91 patients received GM-CSF alone. Patient characteristics—including age, node status, tumor size, hormone receptor status, and HER2 expression—were similar between treatment groups. Both groups initially received six monthly vaccinations and then four boosters every six months.

At a median follow-up of 34 months, there were no recurrences among patients with the highest expression of HER2 who had received the GP2 vaccine. When the researchers analyzed results using an intend-to-treat method (meaning they included results for all patients who should have received a treatment regimen, even those who for whatever reason did not), they found that the disease-free survival rate was higher among those who received the GP2 vaccine: 88% versus 81% for those who received GM-CSF alone. This translated to a 37% reduction in recurrence. When the researchers excluded outcomes for patients who had a recurrence during their primary vaccination series or developed a second malignancy, the disease-free survival rate for patients who received the GP2 vaccine was 94% compared with 85% in unvaccinated patients; this meant that vaccinated patients had a 57% reduction in risk of recurrence. The GP2 vaccine appeared to be well tolerated, with similar toxicity (harmful effects) as GM-CSF alone (most were low grade and improved after taking acetaminophen).

Based on these findings, the GP2 vaccine appears promising in addition to standard therapy in women with HER2-positive breast cancer, as it might have the potential to safely and effectively prevent recurrences. The researchers also speculate that GP2 works with Herceptin in a specific way to stimulate immune response and that further research into this interaction is warranted.4


  2. Peoples G, Khoo S, Dehqanzada Z, et al. Combined Clinical Trial Results of a HER2/neu (E75) Vaccine for Prevention of Recurrence in High-Risk Breast Cancer Patients. Proceedings from the 2006 annual San Antonio Breast Cancer Symposium. Oral presentation December 14, December 2006. Abstract #4.
  3. Peoples GE, Burney JM, Hueman MT et al. Clinical trial results of a HER2/neu (E75) vaccine to prevent recurrence in high-risk breast cancer patients. Journal of Clinical Oncology. Early online publication September 12, 2005.
  4. Schneble EJ, Perez SA, Murray JL, et al. Primary Analysis of the Prospective, Randomized, Phase II Trial of GP2+GM-CSF Vaccine Versus GM-CSF Alone Administered in the Adjuvant Setting to High-Risk Breast Cancer Patients. 2014 Breast Cancer Symposium; September 4–6, 2014; San Francisco, CA. Abstract 134.