| RRC ID |
18739
|
| 著者 |
Fujiwara S, Nawa A, Luo C, Kamakura M, Goshima F, Kondo C, Kiyono T, Kikkawa F, Nishiyama Y.
|
| タイトル |
Carrier cell-based delivery of replication-competent HSV-1 mutants enhances antitumor effect for ovarian cancer.
|
| ジャーナル |
Cancer Gene Ther
|
| Abstract |
Oncolytic viruses capable of tumor-selective replication and cytolysis have shown early promise as cancer therapeutics. We have developed replication-competent attenuated herpes simplex virus type 1 (HSV-1) mutants, named HF10 and Hh101, which have been evaluated for their oncolytic activities. However, the host immune system remains a significant obstacle to effective intraperitoneal administration of these viruses in the clinical setting. In this study, we investigated the use of these HSV-1 mutants as oncolytic agents against ovarian cancer and the use of human peritoneal mesothelial cells (MCs) as carrier cells for intraperitoneal therapy. MCs were efficiently infected with HSV-1 mutants, and MCs loaded with HSV-1 mutants caused cell killing adequately when cocultured with cancer cells in the presence or absence of HSV antibodies. In a mouse xenograft model of ovarian cancer, the injection of infected carrier cells led to a significant reduction of tumor volume and prolonged survival in comparison with the injection of virus alone. Our results indicate that replication-competent attenuated HSV-1 exerts a potent oncolytic effect on ovarian cancer, which may be further enhanced by the utilization of a carrier cell delivery system, based on amplification of viral load and possibly on avoidance of neutralizing antibodies.
|
| 巻・号 |
18(2)
|
| ページ |
77-86
|
| 公開日 |
2011-2-1
|
| DOI |
10.1038/cgt.2010.53
|
| PII |
cgt201053
|
| PMID |
20885447
|
| PMC |
PMC3025316
|
| MeSH |
Animals
Cell Survival / genetics
Female
Herpesvirus 1, Human / genetics*
Herpesvirus 1, Human / physiology
Humans
Mice
Mice, Inbred BALB C
Mice, Nude
Oncolytic Virotherapy / methods*
Oncolytic Viruses / genetics*
Ovarian Neoplasms / genetics
Ovarian Neoplasms / pathology
Ovarian Neoplasms / therapy*
Ovarian Neoplasms / virology
Tumor Cells, Cultured
Virus Replication
Xenograft Model Antitumor Assays
|
| IF |
4.534
|
| 引用数 |
21
|
|
WOS 分野
|
MEDICINE, RESEARCH & EXPERIMENTAL
BIOTECHNOLOGY & APPLIED MICROBIOLOGY
GENETICS & HEREDITY
ONCOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
Vero(RCB0001) |
