The therapeutic promise of oncolytic viruses (OVs) rests on their ability to both selectively kill tumor cells and induce anti-tumor immunity. The potential of tumors to be recognized and eliminated by an effective anti-tumor immune response has been spurred on by the discovery that immune checkpoint inhibition can overcome tumor-specific cytotoxic T cell (CTL) exhaustion and provide durable responses in multiple tumor indications. OV-mediated tumor destruction is now recognized as a powerful means to assist in the development of anti-tumor immunity for two important reasons: (i) OVs, through the elicitation of an anti-viral response and the production of type I interferon, are potent stimulators of inflammation and can be armed with transgenes to further enhance anti-tumor immune responses; and (ii) lytic activity can promote the release of tumor-associated antigens (TAAs) and tumor neoantigens that function as in situ tumor-specific vaccines to elicit adaptive immunity. Oncolytic herpes simplex viruses (oHSVs) are among the most widely studied OVs for the treatment of solid malignancies, and Amgen's oHSV Imlygic® for the treatment of melanoma is the only OV approved in major markets. Here we describe important biological features of HSV that make it an attractive OV, clinical experience with HSV-based vectors, and strategies to increase applicability to cancer treatment.

中文翻译：

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溶瘤 HSV 载体和抗肿瘤免疫。

溶瘤病毒 (OVs) 的治疗前景取决于它们选择性杀死肿瘤细胞和诱导抗肿瘤免疫的能力。免疫检查点抑制可以克服肿瘤特异性细胞毒性 T 细胞 (CTL) 耗竭并在多种肿瘤适应症中提供持久反应的发现激发了通过有效的抗肿瘤免疫反应识别和消除肿瘤的潜力。OV 介导的肿瘤破坏现在被认为是帮助发展抗肿瘤免疫的有力手段，原因有两个：(i) OV 通过引发抗病毒反应和产生 I 型干扰素，是有效的炎症刺激剂，可配备转基因以进一步增强抗肿瘤免疫反应；原位肿瘤特异性疫苗引发适应性免疫。溶瘤单纯疱疹病毒 (oHSV) 是研究最广泛的用于治疗实体恶性肿瘤的 OV 之一，而安进公司用于治疗黑色素瘤的 oHSV Imlygic® 是唯一在主要市场获得批准的 OV。在这里，我们描述了 HSV 的重要生物学特征，使其成为有吸引力的 OV、基于 HSV 的载体的临床经验，以及增加癌症治疗适用性的策略。