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

作者：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^*

来源：Expert Review of Vaccines, 2011, 10(2): 201-210.

DOI：10.1586/ERV.10.167

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

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.

• 出版日期2011-2