...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Medical and Pediatric Oncology: The Official Journal of the American Association for Cancer Education >Immunotherapeutic strategies in neuroblastoma: antitumoral activity of deglycosylated Ricin A conjugated anti-GD2 antibodies and anti-CD3xanti-GD2 bispecific antibodies.
【24h】

Immunotherapeutic strategies in neuroblastoma: antitumoral activity of deglycosylated Ricin A conjugated anti-GD2 antibodies and anti-CD3xanti-GD2 bispecific antibodies.

机译：神经母细胞瘤的免疫治疗策略：去糖基化蓖麻毒蛋白A偶联的抗GD2抗体和抗CD3x抗GD2双特异性抗体的抗肿瘤活性。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

BACKGROUND: The antigen GD2 is selectively expressed on the surface of neuroblastoma cells, and is detected by the monoclonal antibody BW704. In this study, we describe the antitumoral capacity of the immunotoxin BW704dgA (BW704 conjugated to deglycosylated ricin A), and of anti-CD3xanti-GD2 bispecific antibodies that are capable of redirecting cytotoxic T cells towards neuroblastoma cells. We further investigate the in vivo activity of BW704dgA immunotoxins in a human neuroblastoma model in SCID mice. PROCEDURE: BW704dgA immunotoxins were injected i.p. as a single close (48 microg/mouse) on day 4 or divided into three doses on day 4, 5, and 6 after i.v. inoculation of the human neuroblastoma cell line IMR5-75. RESULTS: The mean survival time (MST) of BW704dgA treated animals was significantly increased (MST 49 days) compared to the control animals treated with irrelevant immunotoxin, unconjugated BW704, or control buffer (MST 33 to 39 days, P < 0.0001), without differences in the application schedules. Anti-CD3xanti-NP antibodies and NP-conjugated GD2-antibodies (BW704-NP) were used in a cytotoxicity assay with cytotoxic T-cells as effectors, and tracer labeled neuroblastoma cell line IMR5 as target cells. Anti-CD3xanti-NP antibodies, together with BW704-NP, showed increased cytotoxic activity compared to the incubation with CD3xanti-NP antibodies alone or with unconjugated anti-GD2. Additionally, a dose-dependent effect of NP-conjugated anti-GD2-antibodies upon the lysis of the target cells could be demonstrated. In this report, we describe two immunotherapeutic approaches using GD2 binding BW704 antibodies, modified as immunotoxin and a bispecific antibody, for the targeting and elimination of neuroblastoma cells. CONCLUSIONS: We envisage a combined immunotherapeutic regimen consisting of BW704dgA mediated stem cell purging, followed by a systemic treatment with anti-CD3xanti-GD2 bispecific antibodies in neuroblastoma.
机译：背景：抗原GD2在神经母细胞瘤细胞表面选择性表达，并由单克隆抗体BW704检测。在这项研究中，我们描述了免疫毒素BW704dgA（与去糖基化蓖麻蛋白A结合的BW704）以及能够将细胞毒性T细胞重定向至神经母细胞瘤细胞的抗CD3xanti-GD2双特异性抗体的抗肿瘤能力。我们进一步调查在SCID小鼠的人类神经母细胞瘤模型中BW704dgA免疫毒素的体内活性。程序：腹腔注射BW704dgA免疫毒素。在第4天一次封闭治疗（48微克/小鼠），或在静脉注射后第4、5和6天分为三剂。人神经母细胞瘤细胞系IMR5-75的接种。结果：与不相关免疫毒素，未结合的BW704或对照缓冲液（MST 33至39天，P <0.0001）处理的对照组相比，BW704dgA处理的动物的平均生存时间（MST）显着增加（MST 49天）申请时间表的差异。抗CD3x抗NP抗体和NP缀合的GD2抗体（BW704-NP）用于细胞毒性测定，细胞毒性T细胞作为效应物，示踪剂标记的神经母细胞瘤细胞系IMR5作为靶细胞。与仅与CD3xanti-NP抗体或与未结合的抗GD2孵育相比，抗CD3xanti-NP抗体与BW704-NP共同显示出更高的细胞毒活性。另外，可以证明NP缀合的抗GD2-抗体对靶细胞裂解的剂量依赖性作用。在本报告中，我们描述了两种结合GD2的BW704抗体（经修饰为免疫毒素和双特异性抗体）用于靶向和消除成神经细胞瘤细胞的免疫治疗方法。结论：我们设想了由BW704dgA介导的干细胞清除组成的联合免疫治疗方案，然后在成神经细胞瘤中用抗CD3xanti-GD2双特异性抗体进行全身治疗。

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