The Impact of HER2/neu Expression Level on Response to the E75 Vaccine: From US Military Cancer Institute Clinical Trials Group Study I-01 and I-02
The Impact of HER2/neu Expression Level on Response to the E75 Vaccine: From US Military Cancer Institute Clinical Trials Group Study I-01 and I-02
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DOI：
10.1158/1078-0432.ccr-08-1126
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发表时间：
2009-04-15
影响因子：
11.5
通讯作者：
Peoples, George E.
中科院分区：
文献类型：
--
作者：
Benavides, Linda C.;Gates, Jeremy D.;Peoples, George E.
目的：HER2/neu 是免疫原性肽的来源，在 > 75% 的乳腺癌患者中表达。我们已经在具有不同 HER2/neu 表达水平的乳腺癌患者中进行了 HER2/neu E75 肽疫苗的临床试验。分析基于 HER2/neu 表达水平的疫苗反应。实验设计：根据 HER2/neu 表达对患者进行分层。低表达者 (n = 100) 定义为 HER2/neu 免疫组织化学 (IHC) 1(+) 至 2(+) 或荧光原位杂交 = 2.0。根据 IHC 状态 (0-3(+)) 进行分层进行额外分析。评估了标准临床病理因素、免疫反应（体内迟发型超敏反应；离体人白细胞抗原 A2：免疫球蛋白 G 二聚体测定）和临床反应（复发；死亡率）。 结果：评估了低表达患者（对照，44 例；接种疫苗，56 例）与过度表达患者（对照，22 例；接种疫苗，29 例）。低表达者、过度表达者和大多数 IHC 状态的疫苗接种组均出现免疫反应。与过度表达患者相比，接种疫苗的低表达患者具有更大的最大免疫反应（P = 0.04），而接种疫苗的 IHC 1（+）患者则具有增强的长期免疫反应（P = 0.08）。更重要的是，与对照组相比，低表达蛋白患者的死亡率降低了（P = 0.08）。 lHC 1(+) 患者死亡率下降幅度最大（P = 0.05）。此外，一部分过度表达患者 (n = 7) 在疫苗接种前接受了曲妥珠单抗，这种组合似乎安全且在免疫学上有益。结论：大多数具有不同水平 HER2/neu 表达的患者有免疫反应，并且似乎从疫苗接种中受益。低表达者，特别是 IHC 1(+) 患者，具有更强的免疫反应，可能从 E75 疫苗中获得最大的临床益处。
Purpose: HER2/neu, a source of immunogenic peptides, is expressed in > 75% of breast cancer patients. We have conducted clinical trials with the HER2/neu E75 peptide vaccine in breast cancer patients with varying levels of HER2/neu expression. Vaccine response based on HER2/neu expression level was analyzed.Experimental Design: Patients were stratified by HER2/neu expression. Low expressors (n = 100) were defined as HER2/neu immunohistochemistry (IHC) 1(+) to 2(+) or fluorescence in situ hybridization = 2.0. Additional analyses were done stratifying by IHC status (0-3(+)). Standard clinocopathlogic factors, immunologic response (in vivo delayed-type hypersensitivity reactions; ex vivo human leukocyte antigen A2:immunoglobulin G dimer assay), and clinical responses (recurrence; mortality) were assessed.Results: Low-expressor (control, 44; vaccinated, 56) versus overexpressor patients (control, 22; vaccinated, 29) were assessed. Low expressors, overexpressors, and most IHC-status vaccinated groups responded immunologically. Vaccinated low-expressor patients had larger maximum immunologic responses compared with overexpressor patients (P = 0.04), and vaccinated IHC 1(+) patients had increased long-term immune response (P = 0.08). More importantly, compared with controls, low-expressor patients had a mortality reduction (P = 0.08). The largest decrease in mortality was seen in lHC 1(+) patients (P = 0.05). In addition, a subset of overexpressor patients (n = 7) received trastuzumab before vaccination, and this combination seems safe and immunologically beneficial.Conclusions: Most patients with various levels of HER2/neu expression responded immunologically and seemed to benefit from vaccination. The low expressors, specifically IHC 1(+) patients, had more robust immunologic responses and may derive the greatest clinical benefit from the E75 vaccine.