来自美国圣安东尼奥布鲁克陆军医学中心，德州大学MD安德森癌症研究中心等处的研究人员发表了题为“Clinical trial results of the HER-2/neu (E75) vaccine to prevent breast cancer recurrence in high-risk patients: From US Military Cancer Institute Clinical Trials Group Study I-01 and I-02”的文章，公布一种癌症疫苗：E75的临床实验最新结果，这种疫苗被证明能提高剂量依赖的HER-2/neu免疫，降低高危乳腺癌患者的复发危险。相关成果公布在Cancer杂志上。
领导这一研究的是圣安东尼奥军事医学研究所癌症疫苗研发项目组首席科学家George E. Peoples博士，Peoples博士研究组一直致力于这种癌症疫苗的研究，他们针对E75已进行了约十年的研究分析，Peoples博士表示，癌症疫苗一般的原理是针对癌细胞内某些种类的抗原或蛋白质施加作用，“我们的疫苗让癌症复发率降低了一半”。
就像目前的不少流感病毒疫苗一样，人们也很期待发病率逐年增高的各种癌症也可以有疫苗面试，这样人们就不必如此惧怕癌症。然而，这是一项相当大的医学工程，非一朝一夕就可全部完成的，但幸运地是乳腺癌有可能第一个实现这种小部分的突破。
这种称为E75的疫苗来源于HER-2/neu的免疫源性肽，在乳腺癌细胞中过渡表达，之前的研究就表明HER-2/neu(E75)疫苗预防高危乳腺癌复发，在2009年，这一研究组进行了两项平行临床试验以评价E75的有效性，共纳入186例常规治疗后达无病状态的乳腺癌患者，其中腋窝淋巴结阳性(NP)和阴性(NN)者分别为95例和91例。
研究结果表明E75疫苗对高复发危险的早期乳腺癌患者有益，接受疫苗接种加标准辅助治疗患者的短期转归优于仅接受辅助治疗者。加强免疫有可能改善疫苗特异性免疫衰减，但需要更大样本的试验来证实疫苗有效性。
在最新这项研究成果，研究人员展开了尚具有完好免疫系统的病患的临床实验，这些病人经过治疗已经康复，但是随时存在癌症复发风险的患者。研究人员此次采用的疫苗制品是由E-75肽段和HER2蛋白共同混合制成，并掺入了免疫系统激发药剂。
结果显示，接受疫苗注射的实验组癌症的复发率为10%，而未接受注射的参照组的复发率则高达20%。近期这一研究组还将进行更大规模的实验，将有700至1000名患者参加测试。但和先前的实验不一样的是，这一轮的实验将由一家商业公司：Galena Biopharma承担，这家公司拥有开展此类大规模实验的相关资源和人力。这家公司最后将申请美国食品药品监督管理局的核准，一旦获批，这种新的疫苗即可投放市场。
原文摘要：
Clinical trial results of the HER-2/neu (E75) vaccine to prevent breast cancer recurrence in high-risk patients: From US Military Cancer Institute Clinical Trials Group Study I-01 and I-02
BACKGROUND: The authors conducted exploratory phase 1-2 clinical trials vaccinating breast cancer patients with E75, a human leukocyte antigen (HLA) A2/A3-restricted HER-2/neu (HER2) peptide, and granulocyte-macrophage colony-stimulating factor. The vaccine is given as adjuvant therapy to prevent disease recurrence. They previously reported that the vaccine is safe and effective in stimulating expansion of E75-specific cytotoxic T cells. Here, they report 24-month landmark analyses of disease-free survival (DFS).
METHODS: These dose escalation/schedule optimization trials enrolled lymph node-positive and high-risk lymph node-negative patients with HER2 (immunohistochemistry [IHC] 1-3(+) ) expressing tumors. HLA-A2/A3(+) patients were vaccinated; others were followed prospectively as controls for recurrence. DFS was analyzed by Kaplan-Meier curves; groups were compared using log-rank tests.
RESULTS: Of 195 enrolled patients, 182 were evaluable: 106 (58.2%) in the vaccinated group and 76 (41.8%) in the control group. The 24-month landmark analysis DFS was 94.3% in the vaccinated group and 86.8% in the control group (P = .08). Importantly, because of trial design, 65% of patients received a lower than optimal vaccine dose. In subset analyses, patients who benefited most from vaccination (vaccinated group vs control group) had lymph node-positive (DFS, 90.2% vs 79.1%; P = .13), HER2 IHC 1+-2+ (DFS, 94.0% vs 79.4%; P = .04), or grade 1 or 2 (DFS, 98.4% vs 86.0%; P = .01) tumors and were optimally dosed (DFS, 97.3% vs 86.8%; P = .08). A booster program has been initiated; no patients receiving booster inoculations have recurred.
CONCLUSIONS: The E75 vaccine has clinical efficacy that is more prominent in certain patients. A phase 3 trial enrolling lymph node-positive patients with HER2 low-expressing tumors is warranted. Cancer 2011. © 2011 American Cancer Society
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