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[Killing effect of adenovirus vector-mediated herpes simplex virus thymidine kinase gene recombinant construct on
Jian-Feng Zhou1, Gang Chen, Yun-Ping Lu
1Cancer Molecular Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China.
Background & Objective:
Adenovirus vector-mediated herpes simplex virus thymidine kinase gene (ADV-TK) transfer is one of the major gene therapy strategies for tumor. This study was designed to determine the in vitro anti-tumor efficiency of ADV-TK, a recombinant construct previously developed in our laboratory.
Methods:
Herpes simplex virus thymidine kinase (TK) gene was transduced into 14 types of cultured tumor cells with different histological origins using adenovirus vector followed by ganciclovir (GCV) medication. The killing efficiency was measured using MTT assay.
Results:
At the dosage of 1x10(9) viral particles/per well in the presence of 100 microg/ml GCV, ADV-TK/GCV caused effective killing of 11 out of total 14 types of tumor cells with a rate higher than 74%, the other 3 tumor cells, laryngeal epithelial cancer cells (Hep-2), hepatic cancer cells (Bel7402), and human colon cancer cells (HCT-8) were less sensitive to the ADV-TK/GCV treatment with the killing rates of 55.3%+/-2.0%, 61.3%+/-2.0%, and 63.7%+/-2.5%, respectively. Except for Hep-2, the killing efficiency caused by ADV-TK/GCV treatment was similar to that caused by cisplatin at a dosage equal to the in vivo peak concentration (5 microg/ml) in tissue.
Conclusion:
ADV-TK is highly efficient for active killing of tumor cells in vitro and is promising for future clinical application.
Insights
Adenovirus-mediated herpes simplex virus thymidine kinase (ADV-TK) gene therapy effectively killed 11 of 14 tumor cell types in vitro. This gene therapy shows promise for future clinical applications against various cancers.
Area of Science:
- Oncology
- Gene Therapy
- Virology
Context:
- Adenovirus vector-mediated herpes simplex virus thymidine kinase (ADV-TK) gene transfer is a key strategy in cancer gene therapy.
- Previous research in our lab developed a specific ADV-TK construct for anti-tumor applications.
Purpose:
- To evaluate the in vitro anti-tumor efficacy of the laboratory-developed ADV-TK construct.
- To determine the effectiveness of ADV-TK gene transfer combined with ganciclovir (GCV) against diverse cancer cell lines.
Summary:
- Herpes simplex virus thymidine kinase (TK) gene was delivered to 14 tumor cell types using an adenovirus vector, followed by ganciclovir (GCV) treatment.
- The ADV-TK/GCV combination demonstrated significant tumor cell killing in 11 of 14 cell lines (>74% efficacy) at 1x10(9) viral particles/well and 100 microg/ml GCV.
- Laryngeal, hepatic, and colon cancer cells showed lower sensitivity, with killing rates ranging from 55.3% to 63.7%.
Impact:
- The ADV-TK/GCV treatment showed comparable efficacy to cisplatin in most tested tumor cells, indicating potent anti-cancer activity.
- The study concludes that ADV-TK is highly effective for in vitro tumor cell killing and holds significant potential for clinical translation in cancer therapy.
