Gene-Viral Cancer Therapy Using Dual-Regulated Oncolytic Adenovirus with Antiangiogenesis Gene for Increased Efficacy.
(2008) In Molecular Cancer Research 6. p.568-575- Abstract
- Conditionally replicative adenovirus (CRAD) represents a promising approach for cancer therapy. Several CRADs controlled by the human telomerase reverse transcriptase promoter have been developed. However, because of their replicative capacity, the importance of cancer specificity for CRADs needs to be further emphasized. In this study, we have developed a novel dual-regulated CRAD, CNHK500-mE, which has its E1a and E1b gene controlled by the human telomerase reverse transcriptase promoter and the hypoxia response element, respectively. It also carries a mouse endostatin expression cassette controlled by the cytomegalovirus promoter. These properties allow for increased cancer cell targeting specificity and decreased adverse side effects.... (More)
- Conditionally replicative adenovirus (CRAD) represents a promising approach for cancer therapy. Several CRADs controlled by the human telomerase reverse transcriptase promoter have been developed. However, because of their replicative capacity, the importance of cancer specificity for CRADs needs to be further emphasized. In this study, we have developed a novel dual-regulated CRAD, CNHK500-mE, which has its E1a and E1b gene controlled by the human telomerase reverse transcriptase promoter and the hypoxia response element, respectively. It also carries a mouse endostatin expression cassette controlled by the cytomegalovirus promoter. These properties allow for increased cancer cell targeting specificity and decreased adverse side effects. We showed that CNHK500-mE preferentially replicated in cancer cells. Compared with a replication-defective vector carrying the same endostatin expression cassette, CNHK500-mE-mediated transgene expression level was markedly increased via viral replication within cancer cells. In the nasopharyngeal tumor xenograft model, CNHK500-mE injection resulted in antitumor efficacy at day 7 after therapy. Three weeks later, it led to significant inhibition of xenograft tumor growth due to the combined effects of viral oncolytic therapy and antiangiogenesis gene therapy. Pathologic examination showed that most cancer cells were positive for adenoviral capsid protein and for apoptotic terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling in the CNHK500-mE-treated tumor tissues, and the microvessels in these tumor tissues were diminished in quantity and abnormal in morphology. These results suggest that, as a potential cancer therapeutic agent, the CNHK500-mE is endowed with higher specificity to cancer cells and low cytotoxicity to normal cells. (Mol Cancer Res 2008;6(4):OF1-8). (Less)
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https://lup.lub.lu.se/record/1052414
- author
- organization
- publishing date
- 2008
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Molecular Cancer Research
- volume
- 6
- pages
- 568 - 575
- publisher
- American Association for Cancer Research
- external identifiers
-
- pmid:18344493
- wos:000254905600006
- scopus:42049100962
- pmid:18344493
- ISSN
- 1557-3125
- DOI
- 10.1158/1541-7786.MCR-07-0073
- language
- English
- LU publication?
- yes
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- a6d00f8b-3768-492a-8a58-64faceb46e5a (old id 1052414)
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- http://www.ncbi.nlm.nih.gov/pubmed/18344493?dopt=Abstract
- date added to LUP
- 2016-04-04 09:43:23
- date last changed
- 2022-01-29 19:15:48
@article{a6d00f8b-3768-492a-8a58-64faceb46e5a,
abstract = {{Conditionally replicative adenovirus (CRAD) represents a promising approach for cancer therapy. Several CRADs controlled by the human telomerase reverse transcriptase promoter have been developed. However, because of their replicative capacity, the importance of cancer specificity for CRADs needs to be further emphasized. In this study, we have developed a novel dual-regulated CRAD, CNHK500-mE, which has its E1a and E1b gene controlled by the human telomerase reverse transcriptase promoter and the hypoxia response element, respectively. It also carries a mouse endostatin expression cassette controlled by the cytomegalovirus promoter. These properties allow for increased cancer cell targeting specificity and decreased adverse side effects. We showed that CNHK500-mE preferentially replicated in cancer cells. Compared with a replication-defective vector carrying the same endostatin expression cassette, CNHK500-mE-mediated transgene expression level was markedly increased via viral replication within cancer cells. In the nasopharyngeal tumor xenograft model, CNHK500-mE injection resulted in antitumor efficacy at day 7 after therapy. Three weeks later, it led to significant inhibition of xenograft tumor growth due to the combined effects of viral oncolytic therapy and antiangiogenesis gene therapy. Pathologic examination showed that most cancer cells were positive for adenoviral capsid protein and for apoptotic terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling in the CNHK500-mE-treated tumor tissues, and the microvessels in these tumor tissues were diminished in quantity and abnormal in morphology. These results suggest that, as a potential cancer therapeutic agent, the CNHK500-mE is endowed with higher specificity to cancer cells and low cytotoxicity to normal cells. (Mol Cancer Res 2008;6(4):OF1-8).}},
author = {{Su, Changqing and Na, Manli and Chen, Jie and Wang, Xinghua and Liu, Yongjing and Wang, Weiguo and Zhang, Qi and Li, Linfang and Long, Ju and Liu, Xinyuan and Wu, Mengchao and Fan, Xiaolong and Qian, Qijun}},
issn = {{1557-3125}},
language = {{eng}},
pages = {{568--575}},
publisher = {{American Association for Cancer Research}},
series = {{Molecular Cancer Research}},
title = {{Gene-Viral Cancer Therapy Using Dual-Regulated Oncolytic Adenovirus with Antiangiogenesis Gene for Increased Efficacy.}},
url = {{http://dx.doi.org/10.1158/1541-7786.MCR-07-0073}},
doi = {{10.1158/1541-7786.MCR-07-0073}},
volume = {{6}},
year = {{2008}},
}