Department of Surgery, General Surgery Service, Brooke Army Medical Center, 3851 Roger Brooke Drive, Ft. Sam, Houston, TX 78234, USA.
Expert Rev Vaccines. 2011 Feb;10(2):201-10. doi: 10.1586/erv.10.167.
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.
我们已经进行了多项使用 HER2/neu 蛋白（AE37/E75/GP2）免疫原性肽联合（GM-CSF）皮内给药的辅助临床试验，用于乳腺癌患者。四项试验采用类似的剂量递增设计，增加肽（AE37/E75/GP2）的剂量，并改变 GM-CSF 的用量。对于明显的局部和/或全身毒性，通过减少随后接种的 GM-CSF 进行剂量减少（DR）。使用体外和体内免疫反应来比较组。在 132 名患者中，有 39 名需要 DR（30 名因强烈的局部反应[DR-L]而需要 DR）。DR 患者，尤其是 DR-L，无论是体外还是体内，免疫反应都更强。与其他所有人相比，DR-L 患者的疫苗接种后迟发型超敏反应在 E75（p = 0.001）、AE37（p = 0.077）和 GP2（p = 0.076）方面更大。所有三种肽疫苗均安全且耐受良好。这些发现导致了一种具有临床相关性的最佳疫苗给药策略，该策略可能适用于其他基于肽的癌症疫苗。
