PA Vaccine

[Kim in DC]

Please find below the results thus far for the PA vaccine. The article points out that the 2 women who reoccured had a poor response to the vaccine

Clinical Trial Results of a HER2/neu (E75) Vaccine to Prevent Recurrence in High Risk Breast Cancer Patients

George E. Peoples, MD1,3, Jennifer M. Gurney, MD1, Matthew T. Hueman, MD1, Mike M. Woll, MD1,
Gayle B. Ryan, MD1, Catherine E. Storrer, BS1, Christine Fisher, BS1, Craig D. Shriver, MD1,
Constantine G. Ioannides, PhD2, and Sathibalan Ponniah, PhD1


Running Title: HER2 Vaccine to Prevent Breast Cancer


Funded by the Clinical Breast Care Project, Congressionally funded programs of the Henry M. Jackson Foundation for the Advancement of Military Medicine (Rockville, Maryland).
Supported by the United States Army Medical Research and Development Command,
and the Department of Clinical Investigations at the Walter Reed Army Medical Center.


The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or reflecting the views of the Department of the Army or the Department of Defense.



1Clinical Breast Care Project, Walter Reed Army Medical Center, Washington, DC and Uniformed Services University of the Health Sciences, Bethesda, MD. 2University of Texas MD Anderson Cancer Center, Houston, TX.
3To whom correspondence should be addressed. Department of Surgery, Walter Reed Army Medical Center, 6900 Georgia Ave, NW, Washington, DC 20307-5001. Voice 202-782-9692. Fax 202-782-0759. Email george.peoples@na.amedd.army.mil.

ABSTRACT
Purpose: E75 is an immunogenic peptide from the HER2/neu protein that is highly expressed in breast cancer. We are conducting a clinical trial of an E75 (+GM-CSF) vaccine to assess for safety, immunologic response, and the prevention of clinical recurrences in node-positive breast cancer (NPBC) patients without evidence of disease.
Patients and Methods: Fifty-three NPBC patients have been enrolled thus far and HLA typed. HLA-A2+ patients (n = 24) have been vaccinated while HLA-A2- patients (n = 29) are being followed prospectively as clinical controls. Local/systemic toxicities, immunologic responses, and time to recurrence are being measured.
Results: Only minor toxicities have occurred (one grade 3 (4%)). All patients have demonstrated clonal expansion of E75–specific CD8+ T cells that lysed HER2/neu-expressing tumor cells. An optimal dosage and schedule have been established. Patients have developed DTH reactions to E75 post-vaccination compared to control (33 vs 7 mm, p<0.01). HLA-A2+ patients have been found to have larger, more poorly differentiated, and more hormonally-insensitive tumors compared to the HLA-A2- patients. Despite this, the only two deaths have occurred in the control group. The disease-free survival (DFS) in the vaccinated group is 85.7% compared to 59.8% in the controls at 22 months median follow-up with a recurrence rate of 8% compared to 21%, respectively (p<0.19). Median time to recurrence in the vaccinated patients was prolonged (11 vs 8 months), and recurrence correlated with a weak DTH response.
Conclusion: This HER2/neu (E75) vaccine is safe and effective in eliciting a peptide-specific immune response in vivo. Induced HER2/neu immunity appears to reduce the recurrence rate in high-risk NPBC patients.