scholarly journals Suicide gene therapy against cancer

2021 ◽  
Vol 106 (106(812)) ◽  
pp. 54-65
Author(s):  
C. Piñeiro-Silva

Cancers are a large family of diseases with the highest mortality rate worldwide. Conventional therapies such as chemotherapy or radiotherapy are not efficient in all cases and have important side effects. To solve it, suicide gene therapy can be used. This therapy consists on inducing cell death of cancer cells due to the introduction of a gene. There are three types of this therapy: introduction of a gene encoding generally a bacterial enzyme that actives a prodrug, introduction of a gene encoding a toxin or introduction of a proapoptotic gene. The expression of the targeted gene in tumor cells is produced by using tumor-specific promoters and target vectors. Using those three gene suicide therapies many hallmarks in the field were reached, achieving successful clinical trials and products approved to be used in China (gendicine), achieving apoptosis of tumor cells in vitro and in vivo. Furthermore, several improvements on these techniques were developed due to the mutation of the enzymes and toxins, modification of prodrugs and search of new more active enzymes, toxins and genes, between others. Regardless, further research on this area is needed to guarantee the efficiency of this state-of-the-art therapy and its effectiveness.

2019 ◽  
Vol 21 (7) ◽  
pp. 890-900 ◽  
Author(s):  
Jubayer A Hossain ◽  
Md A Latif ◽  
Lars A R Ystaas ◽  
Sandra Ninzima ◽  
Kristoffer Riecken ◽  
...  

Abstract Background Suicide gene therapy for malignant gliomas has shown encouraging results in the latest clinical trials. However, prodrug application was most often restricted to short-term treatment (14 days), especially when replication-defective vectors were used. We previously showed that a substantial fraction of herpes simplex virus thymidine kinase (HSV-TK) transduced tumor cells survive ganciclovir (GCV) treatment in an orthotopic glioblastoma (GBM) xenograft model. Here we analyzed whether these TK+ tumor cells are still sensitive to prodrug treatment and whether prolonged prodrug treatment can enhance treatment efficacy. Methods Glioma cells positive for TK and green fluorescent protein (GFP) were sorted from xenograft tumors recurring after suicide gene therapy, and their sensitivity to GCV was tested in vitro. GBM xenografts were treated with HSV-TK/GCV, HSV-TK/valganciclovir (valGCV), or HSV-TK/valGCV + erlotinib. Tumor growth was analyzed by MRI, and survival as well as morphological and molecular changes were assessed. Results TK-GFP+ tumor cells from recurrent xenograft tumors retained sensitivity to GCV in vitro. Importantly, a prolonged period (3 mo) of prodrug administration with valganciclovir (valGCV) resulted in a significant survival advantage compared with short-term (3 wk) application of GCV. Recurrent tumors from the treatment groups were more invasive and less angiogenic compared with primary tumors and showed significant upregulation of epidermal growth factor receptor (EGFR) expression. However, double treatment with the EGFR inhibitor erlotinib did not increase therapeutic efficacy. Conclusion Long-term treatment with valGCV should be considered as a replacement for short-term treatment with GCV in clinical trials of HSV-TK mediated suicide gene therapy.


Nanomaterials ◽  
2019 ◽  
Vol 9 (4) ◽  
pp. 573 ◽  
Author(s):  
So-Jung Gwak ◽  
Jeoung Soo Lee

Spinal cord tumors (SCT) are uncommon neoplasms characterized by irregular growth of tissue inside the spinal cord that can result in non-mechanical back pain. Current treatments for SCT include surgery, radiation therapy, and chemotherapy, but these conventional therapies have many limitations. Suicide gene therapy using plasmid encoding herpes simplex virus-thymidine kinase (pHSV-TK) and ganciclovir (GCV) has been an alternative approach to overcome the limitations of current therapies. However, there is a need to develop a carrier that can deliver both pHSV-TK and GCV for improving therapeutic efficacy. Our group developed a cationic, amphiphilic copolymer, poly (lactide-co-glycolide) -graft-polyethylenimine (PgP), and demonstrated its efficacy as a drug and gene carrier in both cell culture studies and animal models. In this study, we evaluated PgP as a gene carrier and demonstrate that PgP can efficiently deliver reporter genes, pGFP in rat glioma (C6) cells in vitro, and pβ-gal in a rat T5 SCT model in vivo. We also show that PgP/pHSV-TK with GCV treatment showed significantly higher anticancer activity in C6 cells compared to PgP/pHSV-TK without GCV treatment. Finally, we demonstrate that PgP/pHSV-TK with GCV treatment increases the suicide effect and apoptosis of tumor cells and reduces tumor size in a rat T5 SCT model.


Oncotarget ◽  
2016 ◽  
Vol 7 (44) ◽  
pp. 71710-71717 ◽  
Author(s):  
De-Gui Wang ◽  
Mei-Jun Zhao ◽  
Yong-Qiang Liu ◽  
Xiang-Wen Liu ◽  
Hai-Tao Niu ◽  
...  

2013 ◽  
Vol 13 (5) ◽  
pp. 346-357 ◽  
Author(s):  
Xiao-Ya Dong ◽  
Wen-Qian Wang ◽  
Yu Zhao ◽  
Xu-Dong Li ◽  
Zhi-Gang Fang ◽  
...  

Blood ◽  
1996 ◽  
Vol 88 (6) ◽  
pp. 2192-2200 ◽  
Author(s):  
MS Dilber ◽  
MR Abedi ◽  
B Bjorkstrand ◽  
B Christensson ◽  
G Gahrton ◽  
...  

Suicide gene therapy for plasma cell tumors was attempted in severe combined immunodeficient (SCID) mice injected with human myeloma cell lines. Initially, a ganciclovir-induced bystander effect was observed in vitro using myeloma cells transduced with a herpes simplex thymidine kinase (HSVtk) gene. Transduced cells injected subcutaneously (SC) into SCID mice could be eradicated by the administration of ganciclovir (GCV). Furthermore, an in vivo bystander effect was noticed when mice received mixtures of HSVtk-positive and nontransduced cells. Unexpectedly, a “distant bystander” effect was observed as tumors in regions inoculated with only nontransduced cells were significantly smaller and had increased frequency of apoptotic figures and decreased mitotic frequency in GCV-treated mice transplanted with HSVtk-positive cells at a different region compared with control mice.


Gene Therapy ◽  
2009 ◽  
Vol 17 (1) ◽  
pp. 26-36 ◽  
Author(s):  
M L Gil-Cardeza ◽  
M S Villaverde ◽  
G L Fiszman ◽  
N A Altamirano ◽  
R A Cwirenbaum ◽  
...  

2012 ◽  
Vol 10 (1) ◽  
pp. 3 ◽  
Author(s):  
Yue Chen ◽  
Gang Wang ◽  
Deling Kong ◽  
Zhihong Zhang ◽  
Kuo Yang ◽  
...  

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