Comparison of different HER2/neuvaccines in adjuvant breast cancer trials: implications for dosing of peptide vaccines
| Autor: | Guy T. Clifton, Jarrod P. Holmes, Jeremy D. Gates, Sathibalan Ponniah, George E. Peoples, Alan K. Sears, Elizabeth A. Mittendorf, Linda C. Benavides, Mark G. Carmichael, Kevin S. Clive |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Receptor
ErbB-2 medicine.medical_treatment Immunology Breast Neoplasms Pharmacology Cancer Vaccines HER2/neu Immune system Breast cancer Adjuvants Immunologic Antigens Neoplasm In vivo Drug Discovery medicine Humans Dosing Clinical Trials as Topic biology business.industry medicine.disease Peptide Fragments Clinical trial Treatment Outcome Vaccines Subunit biology.protein Molecular Medicine Female business Adjuvant Ex vivo |
| Zdroj: | Expert Review of Vaccines. 10:201-210 |
| ISSN: | 1744-8395 1476-0584 |
| DOI: | 10.1586/erv.10.167 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|