ArticleCancer gene therapy2003
Adenovirus-mediated gene transfer of enhanced Herpes simplex virus thymidine kinase mutants improves prodrug-mediated tumor cell killing.
Article in Cancer gene therapy, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 53 citations in OpenAlex.
- The Combinatorial Effect of Ad-IL-24 and Ad-HSV-tk/GCV on Tumor Size, Autophagy, and UPR Mechanisms in Multiple Myeloma Mouse Model.Biochemical genetics · 2025Article
- Engineering and Preclinical Evaluation of Western Reserve Oncolytic Vaccinia Virus Expressing A167Y Mutant Herpes Simplex Virus Thymidine Kinase.Biomedicines · 2020Article
- Conditional Cytotoxic Anti-HIV Gene Therapy for Selectable Cell Modification.Human gene therapy · 2016Article
- Hurdles to clinical translation of human induced pluripotent stem cells.The Journal of clinical investigation · 2015Review
- Genetically engineered theranostic mesenchymal stem cells for the evaluation of the anticancer efficacy of enzyme/prodrug systems.Journal of controlled release : official journal of the Controlled Release Society · 2015Article
- Improved Adeno-associated Viral Gene Transfer to Murine Glioma.Journal of genetic syndromes & gene therapy · 2013Article
- Gene therapy with HSV1-sr39TK/GCV exhibits a stronger therapeutic efficacy than HSV1-TK/GCV in rat C6 glioma cells.TheScientificWorldJournal · 2013Article
- The roles of macrophages and nitric oxide in interleukin-3-enhanced HSV-Sr39tk-mediated prodrug therapy.PloS one · 2013Article
- Frontiers in Suicide Gene Therapy of Cancer.Journal of genetic syndromes & gene therapy · 2012Article
- Retrovolution: HIV-driven evolution of cellular genes and improvement of anticancer drug activation.PLoS genetics · 2012Article
- Enzymes to die for: exploiting nucleotide metabolizing enzymes for cancer gene therapy.Current gene therapy · 2012Review
- Neoadjuvant in situ gene-mediated cytotoxic immunotherapy improves postoperative outcomes in novel syngeneic esophageal carcinoma models.Cancer gene therapy · 2011Article
- Gene therapy and targeted toxins for glioma.Current gene therapy · 2011Review
- HSV-TK/GCV cancer suicide gene therapy by a designed recombinant multifunctional vector.Nanomedicine : nanotechnology, biology, and medicine · 2011Article
- Plant thymidine kinase 1: a novel efficient suicide gene for malignant glioma therapy.Neuro-oncology · 2010Article
- Bystander or no bystander for gene directed enzyme prodrug therapy.Molecules (Basel, Switzerland) · 2009Review
- INSM1 promoter-driven adenoviral herpes simplex virus thymidine kinase cancer gene therapy for the treatment of primitive neuroectodermal tumors.Human gene therapy · 2009Article
- Yeast cytosine deaminase mutants with increased thermostability impart sensitivity to 5-fluorocytosine.Journal of molecular biology · 2008Article
- Genetic strategies for brain tumor therapy.Cancer gene therapy · 2006Review
- Retrovirus-mediated tk gene therapy of implanted human breast cancer in nude mice under the regulation of Tet-On.Cancer gene therapy · 2006Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
The Herpes simplex virus 1 (HSV) thymidine kinase (tk) suicide gene together with ganciclovir (GCV) have been successfully used for the in vivo treatment of various solid tumors and for the ablation of unwanted transfused stem cells in recent clinical trials. With the aim of improving this therapeutic system, we compared the potential efficacy of adenoviral (Ad) vectors expressing enhanced tk mutants in vitro and in vivo. The previously created HSV-tk mutants dm30 and sr39, created by random sequence mutagenesis, were inserted into a standard Ad.RSV E1(-)E3(-) backbone using homologous recombination. GCV killing of Ad.HSV-tk, Ad.dm30-tk and Ad.sr39-tk was assessed in various tumor cell lines with a cell proliferation assay. Cells expressing the two TK mutants were two-to-five-fold more sensitive to GCV when compared with Ad.HSV-tk transduced cells in all cell lines tested (five human mesotheliomas, one human lung cancer, a human cervical carcinoma, a mouse fibrosarcoma, and a rat glioma line) at equal TK expression levels. Flank tumor models, including cell-mixing studies, assessed the in vivo efficacy of the engineered viruses in BALB/C and SCID mice. In all animal studies, Ad.dm30-tk and Ad.sr39-tk showed more tumor growth inhibition than Ad.HSV-tk when GCV was administered. The use of adenovirus-mediated gene transfer of both tk mutants dm30-tk and sr39-tk for cancer suicide gene therapy should provide a more effective and safer alternative to wild-type HSV-tk.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.