Suicide Gene Therapy by Herpes Simplex Virus-1 Thymidine Kinase (HSV-TK)

Dey, Dilip; Evans, Gregory R. D.

doi:10.5772/18544

Cited by 16 publications

(11 citation statements)

References 61 publications

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“…The mechanism is that GCV could be monophosphorylated by HSV‐TK, and then further phosphorylated by the host cell kinase. Triphosphate form of GCV (deoxythymidine triphosphate) is an analog of purine, which inhibits DNA polymerase and is the most toxic to host cell (Dey and Evans, ). T cell overproduction may induce the cytokine release syndrome with features of high‐grade cyclical fevers and hypotension (Morgan et al, ).…”

Section: Discussionmentioning

confidence: 99%

Interleukin‐15‐transferred cytokine‐induced killer cells elevated anti‐tumor activity in a gastric tumor‐bearing nude mice model

Zheng

Liang

et al. 2015

Cell Biology International

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Gastric cancer is the second leading cause of cancer-related mortality worldwide. Adoptive cell therapy (ACT) for gastric cancer is a novel therapy modality. However, the therapeutic effectiveness in vivo is still limited. The objective of this study was to assess the value of interleukin-15 (IL-15)-transferred cytokine-induced killer (CIK) cells in ACT for gastric cancer. IL-15-IRES-TK retroviral vector was constructed and transferred into the CIK cells. A gastric tumor-bearing nude mice model was constructed by subcutaneously injecting gastric cancer cells, BGC-823. Gastric tumor-bearing nude mice were randomly divided into three groups (five mice each group) and injected with physiological saline, CIK cells, and IL-15-IRES-TK-transfected CIK cells for 2 weeks, respectively. IL-15-IRES-TK-transferred CIK cells were prepared successfully and flow cytometry (FCM) analysis indicated that the transfection rate reached 85.7% after 5 days culture. In vivo experiment, we found that CIK cells retarded tumor growth by reducing tumor volume and tumor weight, as well as increasing tumor inhibition rate. Furthermore, IL-15-IRES-TK-transferred CIK cells showed a much stronger inhibition on tumor growth than CIK cells alone. Tumor morphology observation and growth indexes also showed that IL-15-transfected CIK cells had stronger cytotoxicity to tumor tissue than CIK cells. IL-15-IRES-TK transfection could elevate the effects of CIK cells to gastric carcinoma. The engineered CIK cells carrying IL-15-IRES-TK may be used in the ACT for gastric carcinoma, but prudent clinical trial is still indispensable.

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Section: Discussionmentioning

confidence: 99%

Interleukin‐15‐transferred cytokine‐induced killer cells elevated anti‐tumor activity in a gastric tumor‐bearing nude mice model

Zheng

Liang

et al. 2015

Cell Biology International

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“…GCV triphosphate is a deoxyguanosine triphosphate analog, incorporated into the DNA chain causing chain termination and tumor cell death. 73 …”

Section: Chimeric Antigen Receptor (Car) T Cell Therapymentioning

confidence: 99%

The Current Status of Gene Therapy for the Treatment of Cancer

Belete¹

2021

BTT

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Gene therapy is the administration of foreign genomic material into the host tissue to modify the expression of a gene product or to change the biological properties of cells for therapeutic use. Initially, the major objective of gene therapy was to manage genetic diseases, but now different disorders with several patterns of acquired and inherited disorders are targets of gene therapy. Over three decades, the advancement of Genome engineering technologies facilitated gene therapy for the prevention and management of intractable diseases. Researchers are advancing with cautious optimism that safe and effective treatment will give to patients with single-gene disorders and complex acquired disorders. To date, over 3000 genes associates with disease-causing mutations, and about 2600 gene therapy trials are undergoing for the management of various disorders. This review summarizes the principles of genome-editing approaches, such as zinc finger nucleases, transcription activator-like effector nucleases, meganucleases, and the CRISPR/Cas9 system with the underlying mechanisms. This review also explains the types of gene delivery systems as viral [adenoviral, adeno association, herpes simplex virus] and nonviral delivery systems (physical: DNA bombardment, electroporation) and (chemical: Cationic lipids, cationic polymers). Finally, this review summarizes gene therapy medicines approved to treat cancer in detail, including names, indications, vectors, and mode of gene therapy. Gene therapy becomes an alternative to an existing management for different diseases. Therefore, gene products with safe vectors and better biotechnologies play a significant role in the prophylaxis and management of various disorders in the future.

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“…Despite the positive results of this system in several studies, there are some limitations, such as relatively slow kinetics, immunogenicity due to viral origi, and non‐specific toxicity. Furthermore, HSVtk/GCV mainly exerts its bystander effect via gap junctions, while in tumours with cystic and necrotic regions cell‐cell interactions may be reduced or lost, which drastically decreases the efficiency of this treatment 88 …”

Section: Gene Therapy In Hccmentioning

confidence: 99%

“…Furthermore, HSVtk/GCV mainly exerts its bystander effect via gap junctions, while in tumours with cystic and necrotic regions cell-cell interactions may be reduced or lost, which drastically decreases the efficiency of this treatment. 88 CD/5-FC is another suicide gene therapy with a similar rudimentary operating principle to other systems. The bacterial or yeast cytosine deaminase converts 5-fluorocytosine to 5-fluorouracil (5-FU), a highly toxic and diffusible metabolite, which is also used as a chemotherapeutic agent and radiosensitizer.…”

Section: Suicide Gene-based Therapymentioning

confidence: 99%

Advanced therapeutic modalities in hepatocellular carcinoma: Novel insights

Shokoohian

Negahdari

et al. 2021

J Cellular Molecular Medi

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Hepatocellular carcinoma (HCC), the most common type of liver cancer, is usually a latent and asymptomatic malignancy caused by different aetiologies, which is a result of various aberrant molecular heterogeneity and often diagnosed at advanced stages. The incidence and prevalence have significantly increased because of sedentary lifestyle, diabetes, chronic infection with hepatotropic viruses and exposure to aflatoxins. Due to advanced intra‐ or extrahepatic metastasis, recurrence is very common even after radical resection. In this paper, we highlighted novel therapeutic modalities, such as molecular‐targeted therapies, targeted radionuclide therapies and epigenetic modification‐based therapies. These topics are trending headlines and their combination with cell‐based immunotherapies, and gene therapy has provided promising prospects for the future of HCC treatment. Moreover, a comprehensive overview of current and advanced therapeutic approaches is discussed and the advantages and limitations of each strategy are described. Finally, very recent and approved novel combined therapies and their promising results in HCC treatment have been introduced.

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Suicide Gene Therapy by Herpes Simplex Virus-1 Thymidine Kinase (HSV-TK)

Cited by 16 publications

References 61 publications

Interleukin‐15‐transferred cytokine‐induced killer cells elevated anti‐tumor activity in a gastric tumor‐bearing nude mice model

Interleukin‐15‐transferred cytokine‐induced killer cells elevated anti‐tumor activity in a gastric tumor‐bearing nude mice model

The Current Status of Gene Therapy for the Treatment of Cancer

Advanced therapeutic modalities in hepatocellular carcinoma: Novel insights

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