CANCER THERAPY USING ANTIBODY-MEDIATED DELIVERY OF ONCOLYTIC VIRUSES

使用抗体介导的溶瘤病毒递送进行癌症治疗

基本信息

  • 批准号:
    MR/S008578/1
  • 负责人:
  • 金额:
    $ 66.71万
  • 依托单位:
  • 依托单位国家:
    英国
  • 项目类别:
    Research Grant
  • 财政年份:
    2019
  • 资助国家:
    英国
  • 起止时间:
    2019 至 无数据
  • 项目状态:
    未结题

项目摘要

Some viruses that infect humans are currently under investigation for the treatment of cancer; these are referred to as oncolytic viruses. Some of these oncolytic viruses rarely produce serious symptoms in humans while others have been modified so that they no longer cause disease. They act both by directly killing cancer cells and also by stimulating the body's own immune system to attack the cancer. However, with regard to oncolytic viruses, the immune system represents a double-edged sword, because as well as stimulating anti-cancer immune responses, oncolytic viruses also stimulate anti-viral immune responses, including the production of anti-viral neutralizing antibodies. The current perception is that these anti-viral neutralizing antibodies are a barrier to intravenous delivery of oncolytic viruses, because they will neutralize the virus and prevent it reaching the tumour. Thus repeated intravenous injections would be ineffective because of the anti-viral immune response that is generated after the first dose is given to a patient. However, our research has unexpectedly found that neutralizing antibodies may play a role in cancer treatment.We have found that some immune cells in the blood called monocytes can be loaded with pre-formed virus-antibody complexes (so the virus is fully neutralized) and then, by mechanisms not currently known, reactivate the virus so that it can be transferred to tumour cells which it infects and kills. This is very unexpected, as monocytes are thought to destroy all antibody-coated virus they encounter. Our research therefore has significant implications for the future of oncolytic virotherapy and for the design of clinical oncolytic virotherapy treatment strategies.We propose to investigate this further to determine how many of the oncolytic viruses currently under investigation in the clinic, can be reactivated by monocytes in this way. We will also find out whether other cells in the blood can also reactivate antibody-neutralized viruses in the same way as monocytes and investigate the mechanisms involved in the process. This work will increase our understanding of the role of neutralizing antibodies in oncolytic virotherapy and enable improvements in the use of oncolytic viruses for treating cancer.
目前正在研究一些感染人类的​​病毒用于治疗癌症;这些被称为溶瘤病毒。其中一些溶瘤病毒很少在人类中产生严重症状,而另一些则经过修饰,不再引起疾病。它们既可以直接杀死癌细胞,也可以刺激人体自身的免疫系统来攻击癌症。然而,对于溶瘤病毒来说,免疫系统是一把双刃剑,因为溶瘤病毒除了刺激抗癌免疫反应外,还刺激抗病毒免疫反应,包括产生抗病毒中和抗体。目前的看法是,这些抗病毒中和抗体是溶瘤病毒静脉内递送的屏障,因为它们会中和病毒并阻止其到达肿瘤。因此,由于给予患者第一剂后产生的抗病毒免疫反应,重复静脉注射是无效的。然而,我们的研究意外地发现中和抗体可能在癌症治疗中发挥作用。我们发现血液中的一些称为单核细胞的免疫细胞可以装载预先形成的病毒抗体复合物(因此病毒被完全中和),然后通过目前未知的机制重新激活病毒,使其能够转移到它感染和杀死的肿瘤细胞中。这是非常出乎意料的,因为单核细胞被认为可以消灭它们遇到的所有抗体包被的病毒。因此,我们的研究对溶瘤病毒疗法的未来以及临床溶瘤病毒疗法的治疗策略的设计具有重要意义。我们建议进一步研究这一点,以确定目前临床上研究的溶瘤病毒中有多少可以通过这种方式被单核细胞重新激活。我们还将了解血液中的其他细胞是否也可以像单核细胞一样重新激活抗体中和的病毒,并研究该过程中涉及的机制。这项工作将增进我们对中和抗体在溶瘤病毒疗法中作用的理解,并改进溶瘤病毒治疗癌症的用途。

项目成果

期刊论文数量(2)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Past, Present and Future of Oncolytic Reovirus.
  • DOI:
    10.3390/cancers12113219
  • 发表时间:
    2020-10-31
  • 期刊:
  • 影响因子:
    5.2
  • 作者:
    Müller L;Berkeley R;Barr T;Ilett E;Errington-Mais F
  • 通讯作者:
    Errington-Mais F
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Elizabeth Ilett其他文献

Elizabeth Ilett的其他文献

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