Immune checkpoint inhibitors (ICIs) have revolutionized cancer care and shown remarkable efficacy clinically. This efficacy is, however, limited to subsets of patients with significant infiltration of lymphocytes into the tumour microenvironment. To extend their efficacy to patients who fail to respond or achieve durable responses, it is now becoming evident that complex combinations of immunomodulatory agents may be required to extend efficacy to patients with immunologically “cold” tumours. Oncolytic viruses (OVs) have the capacity to selectively replicate within and kill tumour cells, resulting in the induction of immunogenic cell death and the augmentation of anti-tumour immunity, and have emerged as a promising modality for combination therapy to overcome the limitations seen with ICIs. Pre-clinical and clinical data have demonstrated that OVs can increase immune cell infiltration into the tumour and induce anti-tumour immunity, thus changing a “cold” tumour microenvironment that is commonly associated with poor response to ICIs, to a “hot” microenvironment which can render patients more susceptible to ICIs. Here, we review the major viral vector platforms used in OV clinical trials, their success when used as a monotherapy and when combined with adjuvant ICIs, as well as pre-clinical studies looking at the effectiveness of encoding OVs to deliver ICIs locally to the tumour microenvironment through transgene expression.
免疫检查点抑制剂（ICIs）已彻底改变了癌症治疗模式，并在临床上显示出显著疗效。然而，这种疗效仅限于肿瘤微环境中淋巴细胞显著浸润的患者亚群。为了将疗效扩展至无应答或无法获得持久应答的患者，目前日益明确的是，可能需要复杂的免疫调节剂组合方案，才能使免疫学上“冷”肿瘤患者获益。溶瘤病毒（OVs）具有在肿瘤细胞内选择性复制并杀伤肿瘤细胞的能力，可诱导免疫原性细胞死亡并增强抗肿瘤免疫，已成为克服ICIs局限性的联合治疗中极具前景的策略。临床前及临床数据表明，OVs能够增加肿瘤内免疫细胞浸润并诱导抗肿瘤免疫，从而将通常对ICIs反应不佳的“冷”肿瘤微环境转变为“热”微环境，使患者对ICIs更敏感。本文综述了OV临床试验中使用的主要病毒载体平台，其作为单一疗法及与辅助性ICIs联合应用时的成功案例，以及通过转基因表达使编码OVs在肿瘤微环境中局部递送ICIs有效性的临床前研究。
Oncolytic Viruses and Immune Checkpoint Inhibitors: The “Hot” New Power Couple
肿瘤(癌症)患者之家