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

IF 4.8 3区医学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Cancer gene therapy Pub Date : 2025-02-11 DOI:10.1038/s41417-025-00875-y

Erik Yngve, Malin Eriksson, Anders Hedin, Arwa Ali, Chuan Jin, Olle Korsgren, Di Yu

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引用次数: 0

Abstract

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).

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溶瘤腺病毒Adf35（OGN）在叙利亚仓鼠和小鼠体内的生物分布和毒性评价。

溶瘤腺病毒作为一种具有可耐受毒性的癌症治疗剂已被广泛评价。我们最近开发了一种新的溶瘤腺病毒Adf35(OGN)，它含有来自Sus scrofa的α -1,3-半乳糖基转移酶（GGTA1）和来自幽门螺杆菌的中性粒细胞激活蛋白（NAP）两个免疫刺激转基因基因。Adf35（OGN）可以杀死肿瘤细胞并引发针对肿瘤抗原的强烈免疫反应。在这里，我们报告了Adf35（OGN）在叙利亚仓鼠和ggta1敲除小鼠中的毒性和生物分布。以1-5 × 1011病毒颗粒(VP)/kg的剂量给药naïve仓鼠皮下和ggta1敲除小鼠瘤内。病毒没有在任何组织中复制，qPCR检测到的病毒拷贝数很低或没有。在生物体液（唾液、尿液和粪便）中也发现了低水平的病毒，这表明病毒向环境的传播很低，通过脱落继发感染的风险很低。该病毒未引起任何生化、血液学或组织病理学改变。总之，Adf35（OGN）在这些动物模型中具有良好的安全性，这些结果支持Adf35（OGN）未来的临床评估。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cancer gene therapy 医学-生物工程与应用微生物

CiteScore

10.20

自引率

0.00%

发文量

150

审稿时长

4-8 weeks

期刊介绍： Cancer Gene Therapy is the essential gene and cellular therapy resource for cancer researchers and clinicians, keeping readers up to date with the latest developments in gene and cellular therapies for cancer. The journal publishes original laboratory and clinical research papers, case reports and review articles. Publication topics include RNAi approaches, drug resistance, hematopoietic progenitor cell gene transfer, cancer stem cells, cellular therapies, homologous recombination, ribozyme technology, antisense technology, tumor immunotherapy and tumor suppressors, translational research, cancer therapy, gene delivery systems (viral and non-viral), anti-gene therapy (antisense, siRNA & ribozymes), apoptosis; mechanisms and therapies, vaccine development, immunology and immunotherapy, DNA synthesis and repair. Cancer Gene Therapy publishes the results of laboratory investigations, preclinical studies, and clinical trials in the field of gene transfer/gene therapy and cellular therapies as applied to cancer research. Types of articles published include original research articles; case reports; brief communications; review articles in the main fields of drug resistance/sensitivity, gene therapy, cellular therapy, tumor suppressor and anti-oncogene therapy, cytokine/tumor immunotherapy, etc.; industry perspectives; and letters to the editor.