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溶瘤病毒作为抗原非特异性癌症疫苗。

Oncolytic Viruses as Antigen-Agnostic Cancer Vaccines.

机构信息

Department of Molecular Medicine, Mayo Clinic, Rochester, MN 55905, USA.

Department of Cell Biology, University of Miami Miller School of Medicine, Miami, FL 33136, USA.

出版信息

Cancer Cell. 2018 Apr 9;33(4):599-605. doi: 10.1016/j.ccell.2018.03.011.

DOI:10.1016/j.ccell.2018.03.011
PMID:29634947
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5918693/
Abstract

Selective destruction of neoplastic tissues by oncolytic viruses (OVs) leads to antigen-agnostic boosting of neoantigen-specific cytotoxic T lymphocyte (CTL) responses, making OVs ideal companions for checkpoint blockade therapy. Here we discuss the mechanisms whereby OVs modulate both adjuvanticity and antigenicity of tumor cells. Suppression of antitumor immunity after OV therapy has not been observed, possibly because viral antigen expression diminishes as the antiviral response matures, thereby progressively honing the CTL response to tumor neoantigens. By combining direct in situ tumor destruction with the ability to boost antitumor immunity, OVs also have the potential to be powerful standalone cancer therapies.

摘要

溶瘤病毒(OVs)选择性地破坏肿瘤组织,导致新抗原特异性细胞毒性 T 淋巴细胞(CTL)反应的抗原不可知增强,使 OVs 成为检查点阻断治疗的理想伴侣。在这里,我们讨论了 OV 调节肿瘤细胞的佐剂和抗原性的机制。在 OV 治疗后没有观察到抗肿瘤免疫的抑制,这可能是因为随着抗病毒反应的成熟,病毒抗原的表达减少,从而逐渐使 CTL 对肿瘤新抗原的反应得到增强。通过将直接原位肿瘤破坏与增强抗肿瘤免疫的能力相结合,OVs 也有可能成为强大的独立癌症治疗方法。

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Randomized, Open-Label Phase II Study Evaluating the Efficacy and Safety of Talimogene Laherparepvec in Combination With Ipilimumab Versus Ipilimumab Alone in Patients With Advanced, Unresectable Melanoma.随机、开放标签的 II 期研究评估了替莫唑胺联合伊匹单抗与伊匹单抗单药治疗晚期不可切除黑色素瘤患者的疗效和安全性。
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Oncolytic Virotherapy Promotes Intratumoral T Cell Infiltration and Improves Anti-PD-1 Immunotherapy.溶瘤病毒疗法可促进肿瘤内T细胞浸润并改善抗PD-1免疫疗法。
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cGAS surveillance of micronuclei links genome instability to innate immunity.cGAS对微核的监测将基因组不稳定性与先天免疫联系起来。
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