Site Editor

William J. Gradishar, MD, FACP, FASCO


Use of a Plasmid DNA Vaccine in Treatment of Advanced, HER2-Positive Breast Cancer

By: Amy MacDonald, MS
Posted: Monday, February 20, 2023

Favorable clinical outcomes have been reported in patients with breast cancer who develop HER2-specific immunity following trastuzumab therapy. However, only a minority of patients treated with trastuzumab develop this response. To improve immunity to the HER2 antigen, Mary L. (Nora) Disis, MD, of the University of Washington, Seattle, and colleagues evaluated a plasmid DNA vaccine, encoding the entire intracellular domain [ICD] of HER2, in patients with advanced HER2-positive breast cancer. Published in JAMA Oncology, their data demonstrate that this cancer vaccine is safe and associated with the generation of HER2-specific Th1 cells in these patients.

This phase I, nonrandomized, single-institution trial ( identifier NCT00436254) enrolled 66 patients with HER2-positive breast cancer. The study objectives were safety, immunogenicity, and persistent plasmid DNA at the injection site. Three doses of vaccine—10, 100, or 500  mg—were evaluated. The vaccine was administered monthly for 3 months. Toxicity was evaluated for up to 10 years after immunization. Vaccine-related adverse events were grade 1 or 2.

Patients who received 100 mg or 500 mg of vaccine had significantly higher HER2 ICD immune responses than those receiving 10 mg (P = .003) and (P < .001), respectively. The magnitude of HER2 ICD immunity did not significantly differ between patients receiving the two higher doses (P = .77). Of note, the highest dose of vaccine (500 mg) was associated with the greatest persistence of DNA at the injection site, a phenomenon thought by the study authors to be negatively associated with the retention of HER2-specific immunity in the long term.

“We’ve now followed these women for 10 years, and 80% of them are still alive,” Dr. Disis noted in a UW Medicine press release. Phase II trials using 100 mg of HER2 ICD plasmid-based vaccine are now ongoing.

Disclosure: For full disclosures of the study authors, visit

By continuing to browse this site you permit us and our partners to place identification cookies on your browser and agree to our use of cookies to identify you for marketing. Read our Privacy Policy to learn more.