Cotton rat tumor model for the evaluation of oncolytic adenoviruses
Cotton rat tumor model for the evaluation of oncolytic adenoviruses
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DOI：
10.1089/hum.2005.16.139
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发表时间：
2005-01-01
影响因子：
4.2
通讯作者：
Wold, WSM
中科院分区：
文献类型：
--
作者：
Toth, K;Spencer, JF;Wold, WSM
溶瘤人腺病毒 (Ad) 载体通过在肿瘤细胞中复制和裂解肿瘤细胞来发挥抗肿瘤作用。这些载体通常在携带人类肿瘤异种移植物的免疫缺陷小鼠中进行评估。然而，这种模型受到了影响，因为小鼠有免疫缺陷并且不允许人类广告。我们开发了棉鼠模型来测试溶瘤Ad载体的选择性、免疫原性和功效。棉鼠是一种对人类广告半允许的啮齿动物。我们证明，棉癌大鼠细胞系 LCRT 支持组织培养物中人类 Ad 的复制，并且细胞在病毒复制时被破坏。当皮下注射时，LCRT细胞在免疫活性棉鼠中形成肿瘤，并且通过注射溶瘤Ad载体来延迟这些肿瘤的生长。通过在肿瘤内注射病毒后的不同时间对肿瘤组织取样并分离感染性病毒颗粒来证明Ad载体在肿瘤中的复制。我们建议可以使用棉鼠作为动物模型来评估溶瘤Ad载体。
Oncolytic human adenovirus ( Ad) vectors exert their antitumor effect by replicating in and lysing tumor cells. These vectors are commonly evaluated in immunodeficient mice bearing human tumor xenografts. However, this model suffers because the mice are immunodeficient and are not permissive for human Ads. We have developed a cotton rat model to test the selectivity, immunogenicity, and efficacy of oncolytic Ad vectors. The cotton rat is a rodent species that is semipermissive for human Ads. We show that the cotton cancer rat cell line LCRT supports the replication of human Ad in tissue culture and that the cells are destroyed on virus replication. When injected subcutaneously, LCRT cells formed tumors in immunocompetent cotton rats, and the growth of these tumors was delayed by the injection of an oncolytic Ad vector. Replication of the Ad vector in the tumor was demonstrated by sampling tumor tissue and isolating infectious virus particles at various times after intratumoral injection of the virus. We propose that the cotton rat can be used as an animal model to evaluate oncolytic Ad vectors.