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溶瘤免疫病毒治疗:病毒与免疫系统在癌症治疗中的长期相互作用。

Oncolytic ImmunoViroTherapy: A long history of crosstalk between viruses and immune system for cancer treatment.

机构信息

Laboratory of Immunovirotherapy, Drug Research Program, Faculty of Pharmacy, University of Helsinki, Viikinkaari 5E, 00790 Helsinki, Finland; TRIMM, Translational Immunology Research Program, University of Helsinki, Haartmaninkatu 8, 00290 Helsinki, Finland; iCAN Digital Precision Cancer Medicine Flagship, University of Helsinki, Finland.

Laboratory of Immunovirotherapy, Drug Research Program, Faculty of Pharmacy, University of Helsinki, Viikinkaari 5E, 00790 Helsinki, Finland; TRIMM, Translational Immunology Research Program, University of Helsinki, Haartmaninkatu 8, 00290 Helsinki, Finland; iCAN Digital Precision Cancer Medicine Flagship, University of Helsinki, Finland; Department of Molecular Medicine and Medical Biotechnology and CEINGE, Naples University Federico II, S. Pansini 5, 80131 Naples, Italy.

出版信息

Pharmacol Ther. 2022 Aug;236:108103. doi: 10.1016/j.pharmthera.2021.108103. Epub 2021 Dec 23.


DOI:10.1016/j.pharmthera.2021.108103
PMID:34954301
Abstract

Cancer Immunotherapy relies on harnessing a patient's immune system to fine-tune specific anti-tumor responses and ultimately eradicate cancer. Among diverse therapeutic approaches, oncolytic viruses (OVs) have emerged as a novel form of cancer immunotherapy. OVs are a naturally occurring or genetically modified class of viruses able to selectively kill cancer cells, leaving healthy cells unharmed; in the last two decades, the role of OVs has been redefined to act beyond their oncolytic activity. Indeed, the immunogenic cancer cell death mediated by OVs induces the release of tumor antigens that in turn induces anti-tumor immunity, allowing OVs to act as in situ therapeutic cancer vaccines. Additionally, OVs can be engineered for intratumoral delivery of immunostimulatory molecules such as tumor antigens or cytokines to further enhance anti-tumor response. Moreover, OVs can be used in combination with other cancer immunotherapeutic approaches such as Immune Checkpoint Inhibitors and CAR-T cells. The current review first defines the three main mechanisms of action (MOA) of OVs currently used in cancer therapy that are: i) Oncolysis, ii) OV-induced cancer-specific immune activation, and iii) Exploiting pre-existing anti-viral immunity to enhance cancer therapy. Secondly, we focus on how OVs can induce and/or improve anti-cancer immunity in a specific or unspecific fashion, highlighting the importance of these approaches. Finally, the last part of the review analyses OVs combined with other cancer immunotherapies, revising present and future clinical applications.

摘要

癌症免疫疗法依赖于利用患者的免疫系统来微调特定的抗肿瘤反应,并最终消除癌症。在多种治疗方法中,溶瘤病毒 (OVs) 已成为癌症免疫疗法的一种新形式。OVs 是一类天然存在或经过基因改造的病毒,能够选择性地杀死癌细胞,而不会伤害健康细胞;在过去的二十年中,OVs 的作用已被重新定义,超越了其溶瘤活性。事实上,OVs 介导的免疫原性癌细胞死亡会引发肿瘤抗原的释放,进而诱导抗肿瘤免疫,使 OVs 能够作为原位治疗性癌症疫苗发挥作用。此外,OVs 可以被设计用于在肿瘤内递送达免疫刺激分子,如肿瘤抗原或细胞因子,以进一步增强抗肿瘤反应。此外,OVs 可以与其他癌症免疫治疗方法(如免疫检查点抑制剂和 CAR-T 细胞)联合使用。本综述首先定义了目前用于癌症治疗的 OVs 的三种主要作用机制 (MOA),即:i)溶瘤作用、ii)OV 诱导的癌症特异性免疫激活、和 iii)利用预先存在的抗病毒免疫来增强癌症治疗。其次,我们重点关注 OVs 如何以特异性或非特异性方式诱导和/或改善抗肿瘤免疫,强调这些方法的重要性。最后,综述的最后一部分分析了与其他癌症免疫疗法联合使用的 OVs,回顾了当前和未来的临床应用。

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