Comparison of different HER2/neu vaccines in adjuvant breast cancer trials: implications for dosing of peptide vaccines

Abstract

We have performed multiple adjuvant clinical trials using immunogenic peptides from the HER2/neu protein (AE37/E75/GP2) plus (GM-CSF) given intradermally to breast cancer patients. Four trials were performed with similar dose-escalation design with increasing doses of peptide (AE37/E75/GP2) and varying amounts of GM-CSF. Dose reductions (DRs) were made for significant local and/or systemic toxicity by decreasing GM-CSF for subsequent inoculations. Ex vivo and in vivo immunologic responses were used to compare groups. Of 132 patients, 39 required DR (30 for robust local reactions [DR-L]). DR patients, particularly DR-L, had greater immune responses both ex vivo and in vivo. Postvaccine delayed-type hypersensitivity in DR-L patients compared with all others was larger for E75 (p = 0.001), AE37 (p = 0.077) and GP2 (p = 0.076). All three peptide vaccines were safe and well-tolerated. These findings have led to a clinically relevant optimal vaccine dosing strategy, which may be applicable to other peptide-based cancer vaccines.

Keywords::

• AE37 peptide
• dose reduction
• E75 peptide
• GM-CSF
• GP2 peptide
• HER2/neu peptide vaccine

Authors’ note

Article discusses data from the US Military Cancer Institute Clinical Trials Group Studies I-01, I-02, I-03 and I-04 .

Disclaimer

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, the Department of the Navy, or the Department of Defense.

Acknowledgements

The authors gratefully acknowledge the assistance of Katherine Pangaro, Diane Papay, Joyce Winters, Maureen Pavlik and all other clinical nurses of the Cancer Vaccine Development Program (CVDP) for their exceptional patient care. They thank Sathibalan Ponniah, Alexander Stojadinovic, Gayle Ryan, Michael Woll, Jennifer Gurney, Matthew Hueman, Asna Amin, Steven Khoo, Zia Dehqanzada, Elizabeth Mittendorf, Mark Carmichael, Jarrod Holmes, Ritesh Patil, G Travis Clifton, Jeremy Gates and Linda Benavides for their invaluable contributions to database management and data analysis. The authors also thank Jennifer Pappas for her assistance with administrative issues related to the trials. They also sincerely thank Catherine Storrer and the rest of the staff of the Cancer Vaccine Development Lab for their dedicated efforts that have made the fulfillment of the CVDP’s mission possible.

Financial & competing interests disclosure

Supported by the United States Military Cancer Institute, Department of Surgery, Uniformed Services University of the Health Sciences, and the Department of Clinical Investigation, Walter Reed Army Medical Center, Washington DC, USA. Study I-01 and I-02 are primarily funded by the Clinical Breast Care Project. Study I-03 is funded by Antigen Express, Inc., Worchester, MA, USA. This work represents original research that has not been submitted elsewhere for publication. George E Peoples has partial inventor rights to all three vaccines which have been licensed for commercial development based on these results. George E Peoples is entitled to financial proceeds associated with these licenses per Federal policy and may assist these companies in the development of the vaccines. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.