Adenovirus 5（Ad5）具有跨越大多数细胞类型的高效递导和更大的包装能力，因此成为一种引人注目的病毒载体选择。然而，已知已报道过 Ad5 的死亡事件和免疫原性，这也对其使用的安全性产生了质疑。在美国，对于所有采用 Ad5 包装的基因治疗剂量进行肿瘤内注射的临床试验，使用 Common Terminology Criteria for Adverse Events（CTCAE）进行了在线数据库搜索。未明确不良事件（AE）的研究被排除在外。收集的主要结果是≥3级（AE）评分。采用 Fisher's exact test 进行分析。确定了39项前瞻性临床试验，涉及各种癌症；其中14项研究仅使用治疗性 Ad5，12项与化疗、16项与放疗、11项与手术联用。共有3例死亡病例，756名患者中发生（0.4％），其中大部分与 Ad5 无关；由于缺氧性脑病、脾静脉血栓和疾病进展各1例。在报告总 AE（1-5级）的试验中，477名患者中共发生284个（10.3％）≥3级 AE 病例。其中 428 名患者中的 ≈2425 AE 中的总体威胁生命的（评分 4 级）AE 率为1.4％（34/2425 AE）。总体而言，最常见的≥3级AE是淋巴细胞减少症（14项研究，209名患者中的20.6％），呼吸困难（11项研究，208名患者中的8.7％）和中性粒细胞减少症（12项研究，174名患者中的8.6％）。最常见的 4 级 AE 是中性粒细胞减少症（4.6％）、淋巴细胞减少症（3.3％）和白细胞减少症（13项研究，192名患者中的3.1％）。我们的分析表明，Ad5 的整体安全性相对较高，并建议重新评估 Ad5 作为基因治疗产品的传递载体的使用。

With efficient transduction across most cell types and larger packaging capacity, Adenovirus 5 (Ad5) makes an attractive choice as a viral vector. However, a reported past mortality and known immunogenicity cast doubt on the safety of its use. An online database search was performed for all clinical trials administering intratumoral injection of gene therapy packaged in Ad5, being conducted in the United States, and using the Common Terminology Criteria for Adverse Events (CTCAE). Studies with unclear Adverse Events (AE) were excluded. The primary outcome collected was grade ≥3 (AE). Analyses were performed using Fisher's exact test. 39 prospective clinical trials across a variety of cancers were identified; 14 studies of therapeutic Ad5 alone, 12 with chemotherapy, 16 with radiation, and 11 with surgery. There were 3 mortalities out of 756 patients (0.4%) which were most likely unrelated to Ad5; one due to hypoxic encephalopathy, one due to splenic vein thrombus and one due to disease progression. In trials which reported total AE (grades 1-5), there were 284 (10.3%) grade ≥3 AE out of 2745 total AE in 477 patients. The overall life threatening (grade 4) AE rate was 1.4% (34/2425 AE in 428 patients). Overall, the most frequent grade ≥3 AE were lymphopenia (20.6% in 14 trials, 209 patients), dyspnea (8.7% in 11 trials, 208 patients), and neutropenia (8.6% in 12 trials, 174 patients). The most frequent grade 4 AE were neutropenia (4.6%), lymphopenia (3.3%), and leukopenia (3.1% in 13 trials, 192 patients). Our analyses demonstrated relative overall safety of Ad5 and warrants reevaluation for the use of Ad5 as a delivery vector for gene therapy products.