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Research Articles: Therapeutics, Targets, and Development

Biodistribution and kinetics of the novel selective oncolytic adenovirus M1 after systemic administration

Cancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China

Requests for reprints: Jianfeng Zhou or Ding Ma, Cancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, Hubei 430030, People's Republic of China. Phone: 86-27-83662475; Fax: 86-27-83662475. E-mail: jfzhou{at}tjh.tjmu.edu.cn or dina{at}tjh.tjmu.edu.cn

Abstract

Oncolytic adenoviruses represent a promising novel therapeutic option for the treatment of cancer. Despite their demonstrated safety in human clinical trials, the fundamental properties of oncolytic adenovirus biodistribution, spread, viral persistence, and replication in vivo have not been well characterized. The aim of this study was to evaluate the kinetics of viral distribution, spread, replication, and antitumoral efficacy after i.v. administration of a novel oncolytic mutant M1. This mutant consists of the E1A CR2-deleted Adv5 with a fragment of antisense polo-like kinase 1 (plk1) cDNA inserted into the deleted 6.7K/gp19K region, which combines oncolytic properties with efficient plk1 silencing, as described in our previous reports. In the present study, we established a new human orthotopic gastric carcinoma with a high frequency metastasis mouse model and showed that M1 spread not only in local primary tumors but also in disseminated metastases. M1 could effectively replicate in tumor cells leading to "oncolysis" and was able to eliminate expression of the targeted gene plk1 in human orthotopic gastric carcinoma model mice. Therefore, i.v. administration of M1 could prolong the survival time of tumor-bearing mice. [Mol Cancer Ther 2008;7(6):1624–32]

Grant support: National Science Foundation of China grant 30600667; 30770914; 30700895; "973" Program (2002CB513100); "863" Program (2007AA021001).

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Note: X. Huang and L. Zhuang contributed equally to this work.

Received 9/28/07; revised 4/ 6/08; accepted 4/ 8/08.