CVI's WOKVAC, a HER2-directed vaccine, shows promising results in multicenter clinical trial
- Sarah White
- 5 days ago
- 3 min read
The Cancer Vaccine Institute (CVI) was excited to share new results from a multi-center clinical trial led by Moffitt Cancer Center at the 2025 San Antonio Breast Cancer Symposium. These results offer encouraging evidence for WOKVAC, a HER2-targeted DNA vaccine developed here at the CVI. In this study, Moffitt and collaborating sites evaluated whether HER2 vaccination could help prevent recurrence in patients at especially high risk, including individuals who still have invasive cancer remaining after chemotherapy and HER2-targeted therapy before surgery. These patients are known to face a significantly higher chance of cancer returning.
The trial compared two different HER2 vaccines. WOKVAC, developed at the CVI, is a DNA-based vaccine that targets HER2 along with two additional proteins expressed at high levels in breast cancer, IGFBP-2 and IGF1R. After being injected intradermally into the skin, it delivers genetic instructions that prompt the body to temporarily produce small pieces of these proteins, giving the immune system repeated opportunities to learn to recognize them. The second vaccine, DC1, is a dendritic-cell vaccine created by collecting a patient’s own immune cells, exposing them to HER2 in the lab, and then returning them to the patient to stimulate an immune response. This vaccine is injected directly into one of the patient’s lymph nodes to administered.
Across the seven participating cancer centers, including the CVI, 110 patients were enrolled and randomly assigned to receive either WOKVAC or DC1, with vaccine-specific dosing regimens. All had early stage HER2-positive breast cancer with residual disease after neoadjuvant chemotherapy plus HER2-targeted therapy.
Both vaccines were safe and well tolerated, with mostly mild side effects such as injection-site reactions, fatigue, chills, or fever. With more than four years of follow-up, only 11 patients experienced a recurrence – 6 in the DC1 group and 5 in the WOKVAC group. Two of the recurrences in the DC1 arm occurred very early, shortly after enrollment. Overall, recurrence-free survival across both vaccine groups was about 95% at 3 years and around 90% at 5 years. Among patients who also received T-DM1, a standard HER2-targeted therapy now widely used after surgery, recurrence-free survival was even higher – about 96% at both 3 and 5 years.
Immune monitoring showed that both vaccines doubled HER2-specific immune activity one year after vaccination, demonstrating that the immune system remained engaged long after the vaccination series was completed.
These findings are especially meaningful when viewed alongside the landmark KATHERINE trial, which showed that giving T-DM1 instead of trastuzumab alone after surgery reduces the risk of recurrence or death by about 50% in this same high-risk population. The long-term outcomes in this vaccine study are similar to what was achieved with T-DM1, but with far fewer side effects. Based on these results, we believe that adding HER2 vaccination to standard T-DM1 treatment may further improve outcomes for patients who remain at high risk of recurrence.
Building on this work, we at the Cancer Vaccine Institute are now collaborating on additional studies to evaluate whether giving these vaccines alongside HER2-targeted therapies, before or after surgery, can further strengthen anti-tumor immunity and reduce recurrence risk even more.
The Highlights: WOKVAC is a DNA vaccine that targets HER2 and two proteins expressed at high levels with breast cancer. The vaccine delivers genetic instructions for cells to produce small pieces of theses proteins. DC1 is personalized vaccine made from the patient's own immune cells which are exposed to HER2 in the lab and returned to the patient to boost immune response. Overall, recurrence-free survival across both vaccine groups was about 95% at 3 years and 90% at 5 years, When taken with T-DM1, a standard HER2-targeted therapy, about 96% remained cancer-free at both 3 and 5 years. The CVI is now collaborating on additional studies to evaluate whether giving these vaccines alongside HER2-targeted therapies can reduce cancer recurrences even more.
