Surgery, Massachusetts General Hospital and Immuneering Corporation, Boston, Massachusetts, USA.
Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.
J Immunother Cancer. 2020 Oct;8(2). doi: 10.1136/jitc-2020-001486.
Oncolytic viruses (OVs) are a new class of cancer therapeutics. This review was undertaken to provide insight into the current landscape of OV clinical trials. A PubMed search identified 119 papers from 2000 to 2020 with 97 studies reporting data on 3233 patients. The viruses used, presence of genetic modifications and/or transgene expression, cancer types targeted, inclusion of combination strategies and safety profile were reported. In addition, information on viral bioshedding across the studies, including which tissues or body fluids were evaluated and how virus was detected (eg, PCR, plaque assay or both), is also reported. Finally, the number of studies evaluating antiviral and antitumor humoral and cellular immune responses were noted. We found that adenovirus (n=30) is the most common OV in clinical trials with approximately two-thirds (n=63) using modified or recombinant viral backbones and granulocyte-macrophage colony-stimulating factor (n=24) was the most common transgene. The most common tumors targeted were melanoma (n=1000) and gastrointestinal (GI; n=577) cancers with most using monotherapy OVs given by intratumoral (n=1482) or intravenous (n=1347) delivery. The most common combination included chemotherapy (n=36). Overall, OV treatment-related adverse events were low-grade constitutional and local injection site reactions. Viral shedding was frequently measured although many studies restricted this to blood and tumor tissue and used PCR only. While most studies did report antiviral antibody titers (n=63), only a minority of studies reported viral-specific T cell responses (n=10). Tumor immunity was reported in 48 studies and largely relied on general measures of immune activation (eg, tumor biopsy immunohistochemistry (n=25) and serum cytokine measurement (n=19)) with few evaluating tumor-specific immune responses (n=7). Objective responses were reported in 292 (9%) patients and disease control was achieved in 681 (21.1%) patients, although standard reporting criteria were only used in 53% of the trials. Completed clinical trials not reported in the peer-reviewed literature were not included in this review potentially underestimating the impact of OV treatment. These data provide insight into the current profile of OV clinical trials reporting and identifies potential gaps where further studies are needed to better define the role of OVs, alone and in combination, for patients with cancer.
溶瘤病毒(OVs)是一类新型的癌症治疗药物。本综述旨在深入了解 OV 临床试验的现状。通过 PubMed 搜索,从 2000 年到 2020 年共确定了 119 篇论文,其中 97 项研究报告了 3233 例患者的数据。报告了所用的病毒、遗传修饰和/或转基因表达、靶向的癌症类型、联合策略的纳入以及安全性概况。此外,还报告了关于病毒脱落的信息,包括评估哪些组织或体液以及如何检测病毒(例如,PCR、噬菌斑分析或两者兼有)。最后,还注意到了评估抗病毒和抗肿瘤体液及细胞免疫反应的研究数量。我们发现,腺病毒(n=30)是临床试验中最常见的 OV,其中约三分之二(n=63)使用了修饰或重组病毒骨架,粒细胞-巨噬细胞集落刺激因子(n=24)是最常见的转基因。最常见的靶向肿瘤是黑色素瘤(n=1000)和胃肠道(GI;n=577)癌症,大多数采用单药 OV 通过瘤内(n=1482)或静脉内(n=1347)给药。最常见的联合治疗包括化疗(n=36)。总体而言,OV 治疗相关的不良事件是轻度的全身性和局部注射部位反应。病毒脱落经常被测量,尽管许多研究仅限于血液和肿瘤组织,并且仅使用 PCR。虽然大多数研究报告了抗病毒抗体滴度(n=63),但只有少数研究报告了病毒特异性 T 细胞反应(n=10)。48 项研究报告了肿瘤免疫,主要依赖于免疫激活的一般指标(例如,肿瘤活检免疫组化(n=25)和血清细胞因子测量(n=19)),很少评估肿瘤特异性免疫反应(n=7)。报告了 292 例(9%)患者有客观反应,681 例(21.1%)患者达到疾病控制,尽管只有 53%的试验使用了标准报告标准。本综述未包括在同行评议文献中报告的已完成临床试验,这可能低估了 OV 治疗的影响。这些数据深入了解了 OV 临床试验报告的当前概况,并确定了需要进一步研究的潜在差距,以便更好地定义 OV 在癌症患者中的单独和联合作用。