...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Journal of Translational Medicine >Long term disease-free survival and T cell and antibody responses in women with high-risk Her2+ breast cancer following vaccination against Her2
【24h】

Long term disease-free survival and T cell and antibody responses in women with high-risk Her2+ breast cancer following vaccination against Her2

机译：在对HER2疫苗接种后，长期无疾病的存活和T细胞和T细胞和抗体反应在高风险的HER2 +乳腺癌中患者

获取原文
   

获取外文期刊封面封底 >>

       
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Background The HER2-inhibiting antibody trastuzumab, in combination with chemotherapy, significantly improves survival of women with resected, HER2-overexpressing breast cancers, but is associated with toxicities including a risk of cardiomyopathy. Additionally, the beneficial effect of trastuzumab is expected to decrease once the drug is discontinued. We proposed to address these concerns by using cancer vaccines to stimulate HER2 intracellular domain (ICD)-specific T cell and antibody responses. Methods Subjects with stage II (≥ 6 +LN), III, or stage IV breast cancerwith > 50% HER2 overexpressing tumor cells who were disease-free after surgery and adjuvant therapy were eligible. Vaccines consisted of immature, cultured DC (n = 3), mature cultured DC (n = 3), or mature Flt3-ligand mobilized peripheral blood DC (n = 1) loaded with ICD, or tetanus toxoid, keyhole limpet hemocyanin or CMV peptide as controls, and were administered intradermally/subcutaneously four times at 3 week intervals. ICD-specific T cell and antibody responses were measured. Cardiac function was determined by MUGA or ECHO; long term disease status was obtained from patient contact. Results All seven patients successfully underwent DC generation and five received all 4 immunizations. There were no toxicities greater than grade 1 or ejection fraction decrements below normal. Delayed-type hypersensitivity (DTH) reactions at the injection site occurred in 6/7 patients and HER2 specificity was detected by cytokine flow cytometry or ELISPOT in 5 patients. At more than 5 years of follow-up, 6/7 had detectable anti-ICD antibodies. One patient experienced a pulmonary recurrence at 4 years from their study immunizations. This recurrence was resected and they are without evidence of disease. All patients are alive and disease-free at 4.6–6.7 years of follow-up. Conclusion Although this was a small pilot study, the well-tolerated nature of the vaccines, the lack of cardiac toxicity, significant immunogenicity, and a 100% 4.5-year survival rate suggest that vaccination with HER2 ICD protein-containing DC is appropriate for further study in this population. Trial Registration ClinicalTrials.gov NCT00005956
机译：背景技术Her2抑制抗体曲妥珠单抗与化疗组合，显着改善了妇女的生存，患有切除的Her2过度抑制的乳腺癌，但与包括心肌病风险的毒性有关。此外，一旦药物停止，曲妥珠单抗的有益作用将降低。我们建议通过使用癌症疫苗来解决这些问题，刺激HER2细胞内结构域（ICD）特异性T细胞和抗体反应。方法具有阶段II（≥6+ LN），III或阶段IV乳腺癌的方法> 50％HER2过表达肿瘤细胞均有无病和佐剂治疗的肿瘤细胞。疫苗组成，由未成熟，培养的DC（n = 3），成熟培养的DC（n = 3），或成熟的FLT3-配体动员外周血DC（n = 1），其装载ICD，或破伤风毒素，孔孔血红蛋白或CMV肽作为对照，并以3周间隔内/皮下注射4次。测定ICD特异性T细胞和抗体应答。心脏功能由Muga或Echo确定;从患者接触获得长期疾病状态。结果所有7名患者成功接受了直流发电，五个接受了所有4名免疫。没有毒性大于1级或射血分数低于正常情况。通过细胞因子流式细胞术或5例患者检测到6/7患者和HER2特异性的延迟型超敏反应（DTH）反应。在超过5年的随访中，6/7可检测到可检测的抗ICD抗体。一名患者从他们的研究免疫4年内经历了肺部复发。切除这种复发，他们没有疾病的证据。所有患者均为4.6-6.7岁的疾病。结论虽然这是一个小型试验研究，但疫苗的良好耐受性，缺乏心脏毒性，显着的免疫原性和100％4.5年的存活率表明，含HER2含ICD蛋白的DC的疫苗接种适用于进一步的疫苗在这个人口中的研究。试用注册ClinicalTrials.gov NCT00005956

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号