Comparison of different HER2/neu vaccines in adjuvant breast cancer trials: implications for dosing of peptide vaccines. (February 2011)

• Record Type: Journal Article
• Authors: Benavides, Linda C; Sears, Alan K; Gates, Jeremy D; Clifton, Guy T; Clive, Kevin S; Carmichael, Mark G; Holmes, Jarrod P; Mittendorf, Elizabeth A; Ponniah, Sathibalan; Peoples, George E
• Is Part Of: Expert review of vaccines. Volume 10:Number 2(2011)
• Page Start: 201
• Page End: 210
• Publication Date: 2011-02
• Subjects: AE37 peptide -- dose reduction -- E75 peptide -- GM-CSF -- GP2 peptide -- HER2/neu peptide vaccine; Vaccines -- Periodicals; Vaccination -- Periodicals; 615.37205
• DOI: 10.1586/erv.10.167
• Languages: English
• ISSNs: 1476-0584

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.