| RRC ID |
38437
|
| Author |
Yao X, Yoshioka Y, Morishige T, Eto Y, Narimatsu S, Kawai Y, Mizuguchi H, Gao JQ, Mukai Y, Okada N, Nakagawa S.
|
| Title |
Tumor vascular targeted delivery of polymer-conjugated adenovirus vector for cancer gene therapy.
|
| Journal |
Mol Ther
|
| Abstract |
Previously, we generated a cancer-specific gene therapy system using adenovirus vectors (Adv) conjugated to polyethylene glycol (Adv-PEG). Here, we developed a novel Adv that targets both tumor tissues and tumor vasculatures after systemic administration by conjugating CGKRK tumor vasculature homing peptide to the end of a 20-kDa PEG chain (Adv-PEG(CGKRK)). In a primary tumor model, systemic administration of Adv-PEG(CGKRK) resulted in ~500- and 100-fold higher transgene expression in tumor than that of unmodified Adv and Adv-PEG, respectively. In contrast, the transgene expression of Adv-PEG(CGKRK) in liver was about 400-fold lower than that of unmodified Adv, and was almost the same as that of Adv-PEG. We also demonstrated that transgene expression with Adv-PEG(CGKRK) was enhanced in tumor vessels. Systemic administration of Adv-PEG(CGKRK) expressing the herpes simplex virus thymidine kinase (HSVtk) gene (Adv-PEG(CGKRK)-HSVtk) showed superior antitumor effects against primary tumors and metastases with negligible side effects by both direct cytotoxic effects and inhibition of tumor angiogenesis. These results indicate that Adv-PEG(CGKRK) has potential as a prototype Adv with suitable efficacy and safety for systemic cancer gene therapy against both primary tumors and metastases.
|
| Volume |
19(9)
|
| Pages |
1619-25
|
| Published |
2011-9-1
|
| DOI |
10.1038/mt.2011.112
|
| PII |
S1525-0016(16)32747-2
|
| PMID |
21673661
|
| PMC |
PMC3182347
|
| MeSH |
Adenoviridae / genetics*
Animals
Cell Line, Tumor
Gene Expression Regulation
Gene Transfer Techniques
Genes, Viral
Genetic Therapy / methods*
Genetic Vectors*
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Polyethylene Glycols / chemistry
Polyethylene Glycols / therapeutic use
Simplexvirus / genetics
Simplexvirus / metabolism
Thymidine Kinase / genetics
Thymidine Kinase / metabolism
Transduction, Genetic
Transgenes
Vascular Neoplasms / therapy*
|
| IF |
8.986
|
| Times Cited |
25
|
|
WOS Category
|
MEDICINE, RESEARCH & EXPERIMENTAL
BIOTECHNOLOGY & APPLIED MICROBIOLOGY
GENETICS & HEREDITY
|
| Resource |
| Human and Animal Cells |
B16/BL6(RCB2638) |
