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Potent anti-tumor activity of telomerase-dependent and HSV-TK armed oncolytic adenovirus for non-small cell lung cancer in vitro and in vivo.

ABSTRACT:

Background

Non-small cell lung cancer (NSCLC) is the leading cause of cancer related mortality, any improvements in therapeutic strategies are urgently required. In this study we generated a novel 'suicide gene' armed oncolytic adenoviral vector and investigated its antitumor effect both in vitro and in vivo.

Methods

Since the up-regulated expression of human telomerase reverse transcriptase (hTERT) is a hallmark of alltypes of NSCLC, we chose hTERT promoter to transcriptionally control E1A gene expression to obtain adenoviral replication in NSCLC. In order to further enhance anti-tumor effect of this oncolytic adenoviral vector, we inserted a 'suicide gene' i.e. Herpes Simplex Virus Thymidine Kinase (HSV-TK) into oncolytic adenoviral vector to engineer a novel armed oncolytic adenoviral vector 'Ad.hTERT-E1A-TK'.

Results

Ad.hTERT-E1A-TK efficiently killed different types of tumor cells including two types of NSCLC cells in vitro, causing no damage to normal primary fibroblasts. Furthermore, Ad.hTERT-E1A-TK infection combined with administration of prodrug gancyclovir (GCV) resulted in more potent cytotoxicity on NSCLC cells, and synergistically suppressed human NSCLC tumor growth in nude mice.

Conclusion

The results from this study showed that Ad.hTERT-E1A-TK/GCV could be a potent but safe anti-tumor strategy for NSCLC biotherapy.

SUBMITTER: Zhang JF

PROVIDER: S-EPMC2890545 | biostudies-literature | 2010 May

REPOSITORIES: biostudies-literature

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Publications

Potent anti-tumor activity of telomerase-dependent and HSV-TK armed oncolytic adenovirus for non-small cell lung cancer in vitro and in vivo.

Zhang Ju-Feng JF Wei Fang F Wang Hui-Ping HP Li Hui-Ming HM Qiu Wei W Ren Peng-Kang PK Chen Xia-Fang XF Huang Qian Q

Journal of experimental & clinical cancer research : CR 20100520

<h4>Background</h4>Non-small cell lung cancer (NSCLC) is the leading cause of cancer related mortality, any improvements in therapeutic strategies are urgently required. In this study we generated a novel 'suicide gene' armed oncolytic adenoviral vector and investigated its antitumor effect both in vitro and in vivo.<h4>Methods</h4>Since the up-regulated expression of human telomerase reverse transcriptase (hTERT) is a hallmark of alltypes of NSCLC, we chose hTERT promoter to transcriptionally c ...[more]

PMID: 20487549

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Project description:BackgroundSystemic administration of oncolytic adenovirus for cancer therapy is still a challenge. Mesenchymal stem cells as cell carriers have gained increasing attention in drug delivery due to their excellent tumor tropism, immunosuppressive modulatory effects, and paracrine effects. However, the potential of human dental pulp stem cells (hDPSCs) loaded with oncolytic adenovirus for cancer biotherapy has not been investigated yet.MethodsThe stemness of hDPSCs was characterized by FACS analysis and Alizarin red staining, Oil Red O staining, and immunofluorescence assays. The biological fitness of hDPSCs loaded with oncolytic adenovirus YSCH-01 was confirmed by virus infection with different dosages and cell viability CCK-8 assays. Additionally, the expression of CAR receptor in hDPSCs was detected by qPCR assay. Tumor tropism of hDPSC loaded with YSCH-01 in vitro and in vivo was investigated by Transwell assays and living tumor-bearing mice imaging technology and immunohistochemistry, Panoramic scanning of frozen section slices assay analysis. Furthermore, the antitumor efficacy was observed through the different routes of YSCH-01/hPDSCs administration in SW780 and SCC152 xenograft models. The direct tumor cell-killing effect of YSCH-01/hDPSCs in the co-culture system was studied, and the supernatant of YSCH-01/hDPSCs inhibited cell growth was further analyzed by CCK-8 assays.ResultshDPSCs were found to be susceptible to infection by a novel oncolytic adenovirus named YSCH-01 and were capable of transporting this virus to tumor sites at 1000 VP/cell infectious dosage in vitro and in vivo. Moreover, it was discovered that intraperitoneal injection of hDPSCs loaded with oncolytic adenovirus YSCH-01 exhibited potential anti-tumor effects in both SW780 and SCC152 xenograft models. The crucial role played by the supernatant secretome derived from hDPSCs loaded with YSCH-01 significantly exerted a specific anti-tumor effect without toxicity for normal cells, in both an active oncolytic virus and an exogenous protein-independent manner. Furthermore, the use of hDPSCs as a cell carrier significantly reduced the required dosage of virus delivery in vivo compared to other methods.ConclusionsThese findings highlight the promising clinical potential of hDPSCs as a novel cell carrier in the field of oncolytic virus-based anti-cancer therapy.

Dataset Information

Potent anti-tumor activity of telomerase-dependent and HSV-TK armed oncolytic adenovirus for non-small cell lung cancer in vitro and in vivo.

Background

Methods

Results

Conclusion

Publications

Potent anti-tumor activity of telomerase-dependent and HSV-TK armed oncolytic adenovirus for non-small cell lung cancer in vitro and in vivo.

Similar Datasets

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