Department of Bioengineering, College of Engineering, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, Korea.
GeneMedicine Co., Ltd., 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, Korea.
Int J Mol Sci. 2020 Nov 16;21(22):8627. doi: 10.3390/ijms21228627.
Immuno-oncology (IO) has been an active area of oncology research. Following US FDA approval of the first immune checkpoint inhibitor (ICI), ipilimumab (human IgG1 k anti-CTLA-4 monoclonal antibody), in 2011, and of the first oncolytic virus, Imlygic (talimogene laherparepvec), in 2015, there has been renewed interest in IO. In the past decade, ICIs have changed the treatment paradigm for many cancers by enabling better therapeutic control, resuming immune surveillance, suppressing tumor immunosuppression, and restoring antitumor immune function. However, ICI therapies are effective only in a small subset of patients and show limited therapeutic potential due to their inability to demonstrate efficacy in 'cold' or unresponsive tumor microenvironments (TMEs). Relatedly, oncolytic viruses (OVs) have been shown to induce antitumor immune responses, augment the efficacy of existing cancer treatments, and reform unresponsive TME to turn 'cold' tumors 'hot,' increasing their susceptibility to checkpoint blockade immunotherapies. For this reason, OVs serve as ideal complements to ICIs, and multiple preclinical studies and clinical trials are demonstrating their combined therapeutic efficacy. This review will discuss the merits and limitations of OVs and ICIs as monotherapy then progress onto the preclinical rationale and the results of clinical trials of key combination therapies.
免疫肿瘤学（IO）一直是肿瘤学研究的活跃领域。继 2011 年美国食品和药物管理局（FDA）批准首个免疫检查点抑制剂（ICI）——伊匹单抗（抗 CTLA-4 人源 IgG1k 单克隆抗体），以及 2015 年批准首个溶瘤病毒——替莫唑胺（talimogene laherparepvec）之后，IO 领域又重新引起了人们的兴趣。在过去的十年中，ICI 通过更好的治疗控制、恢复免疫监测、抑制肿瘤免疫抑制和恢复抗肿瘤免疫功能，改变了许多癌症的治疗模式。然而，由于其在“冷”或无反应性肿瘤微环境（TME）中无法显示疗效，ICI 疗法仅对一小部分患者有效，且显示出有限的治疗潜力。相关地，溶瘤病毒（OVs）已被证明可诱导抗肿瘤免疫反应，增强现有癌症治疗的疗效，并重塑无反应性 TME，使“冷”肿瘤“热”化，增加其对检查点阻断免疫疗法的敏感性。出于这个原因，OVs 是 ICI 的理想补充，并且多项临床前研究和临床试验正在证明它们的联合治疗疗效。这篇综述将讨论 OVs 和 ICI 作为单一疗法的优缺点，然后探讨关键联合疗法的临床前原理和临床试验结果。
