文章：

溶瘤腺病毒Adf35(OGN)在叙利亚仓鼠和小鼠中的生物分布与毒性评估

Biodistribution and toxicity evaluation of oncolytic adenovirus Adf35(OGN) in Syrian hamster and mouse 

原文发布日期：2025-02-11 

英文摘要：

Oncolytic adenovirus has been widely evaluated as a cancer treatment agent with tolerable toxicity profile. We have recently developed a new oncolytic adenovirus Adf35(OGN) with two immunostimulatory transgenes alpha-1,3-galactosyltransferase (GGTA1) from Sus scrofa and neutrophil-activating protein (NAP) from Helicobacter pylori. Adf35(OGN) can kill tumor cells and trigger a strong immune response against tumor antigens. Here, we report the toxicity and biodistribution of Adf35(OGN) in Syrian hamster and GGTA1-knockout mouse. The virus was delivered subcutaneously in naïve hamsters and intratumorally in GGTA1-knockout mouse in multiple doses at dosages of 1–5 × 1011 viral particles (VP)/kg. The virus did not replicate in any tissues, evidenced as low or no viral copies detected by qPCR. The virus was also found at low levels in biofluids (saliva, urine, and feces), indicating that spread to the environment is low with a low risk of secondary infections via shedding. The virus did not cause any biochemical, hematological, or histopathological alterations. In summary, Adf35(OGN) has a good safety profile in these animal models and these results support future clinical evaluation for Adf35(OGN). 

摘要翻译：

溶瘤腺病毒作为一种癌症治疗剂已被广泛评估，且具有可耐受的毒性特征。我们近期开发了一种新型溶瘤腺病毒Adf35(OGN)，其携带两种免疫刺激转基因：源自Sus scrofa（野猪）的α-1,3-半乳糖基转移酶（GGTA1）和源自幽门螺杆菌的中性粒细胞激活蛋白（NAP）。Adf35(OGN)能杀伤肿瘤细胞并引发针对肿瘤抗原的强烈免疫反应。本文报告了Adf35(OGN)在叙利亚仓鼠和GGTA1基因敲除小鼠体内的毒性及生物分布特性。通过多次皮下注射（naïve仓鼠）和瘤内注射（GGTA1敲除小鼠）方式给药，剂量为1–5×10¹¹病毒颗粒（VP）/公斤。qPCR检测显示病毒在所有组织中均未复制，表现为低拷贝或无可检测病毒拷贝。在生物体液（唾液、尿液和粪便）中病毒含量亦处于低水平，表明环境传播风险较低，通过病毒脱落引发继发感染的可能性小。该病毒未引起任何生化、血液学或组织病理学改变。综上所述，Adf35(OGN)在这些动物模型中展现出良好的安全性特征，此结果支持其开展后续临床评估。

原文链接：

Biodistribution and toxicity evaluation of oncolytic adenovirus Adf35(OGN) in Syrian hamster and mouse