Biodistribution and kinetics of the novel selective oncolytic adenovirus M1 after systemic administration.
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.
Cancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.
Xiaoyuan
X
Huang
Liang
L
Zhuang
Yang
Y
Cao
Qinglei
Q
Gao
Zhiqiang
Z
Han
Duozhuang
D
Tang
Hui
H
Xing
Wei
W
Wang
Yunping
Y
Lu
Gang
G
Xu
Shixuan
S
Wang
Jianfeng
J
Zhou
Ding
D
Ma
D000256:Adenoviridae / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D007700:Kinetics; D051379:Mice; D008807:Mice, Inbred BALB C; D009336:Necrosis; D009362:Neoplasm Metastasis; D050504:Oncolytic Viruses / Q000378:metabolism* / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D013274:Stomach Neoplasms / Q000201:enzymology / Q000473:pathology / Q000821:virology; D013997:Time Factors; D014779:Virus Replication; D023041:Xenograft Model Antitumor Assays; D000097869:Polo-Like Kinase 1
D018797:Cell Cycle Proteins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D000097869:Polo-Like Kinase 1