HSV-tk expressing mesenchymal stem cells exert bystander effect on human glioblastoma cells

Matúšková, Miroslava; Hlubinová, K; Pastorakova, Andrea; Hunáková, Ľuba; Altanerová, Veronika; Altaner, Č; Kučerová, Lucia

doi:10.1016/j.canlet.2009.08.028

Cited by 155 publications

(120 citation statements)

References 27 publications

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“…This lack of success is attributed to the poor transduction of the HSV1 TK gene to the tumor, and the fact that transduction lacks target specificity. Recent approaches, which aim to improve transduction efficiency, to specifically target the tumor, and also to reduce immunogenicity include recombinant non-viral vectors, mesenchymal stem cells, and the use of Bifidobacterium as gene delivery vehicle [29][30][31]. Furthermore, extensive structural and kinetic studies of HSV1 TK have focused on improving the catalytic activity of HSV1 TK for ACV and GCV as substrates [18][19][20][21][22].…”

Section: Discussionmentioning

confidence: 99%

A designed equine herpes thymidine kinase (EHV4 TK) variant improves ganciclovir-induced cell-killing

McSorley

Ort

Monnerjahn

et al. 2014

Biochemical Pharmacology

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Section: Discussionmentioning

confidence: 99%

A designed equine herpes thymidine kinase (EHV4 TK) variant improves ganciclovir-induced cell-killing

McSorley

Ort

Monnerjahn

et al. 2014

Biochemical Pharmacology

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“…MSCs are used as vehicles for targeted anticancer therapy by using the mechanism of enzyme prodrug conversion [59][60][61][62][63][64]. The basic of this mechanism is the conversion of a prodrug (which has low toxicity) to a high toxic metabolite (produced only at tumor site) where the reaction is catalyzed by enzymes [65,66].…”

Section: Mscs Engineered As Anticancer Drug De-livery Systemsmentioning

confidence: 99%

Perspectives in Engineered Mesenchymal Stem/Stromal Cells Based Anti- Cancer Drug Delivery Systems

Ackova¹,

Kanjevac²,

Rimondini³

et al. 2016

PRA

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Understanding and apprehension of the characteristics and circumstances in which mesenchymal stem cells (MSCs) affect and make alterations (enhance or reduce) to the growth of tumors and metastasis spread is pivotal, not only for reaching the possibility to employ MSCs as drug delivery systems, but also for making forward movement in the existing knowledge of involvement of major factors (tumor microenvironment, soluble signaling molecules, etc.) in the process of carcinogenesis. This capability is reliable because MSCs present a great basis for engineering and constructions of new systems to target cancers, intended to secrete therapeutic proteins in the tumor region, or for delivering of oncolytic viruses' directly at the tumor site (targeted chemotherapy with enzyme prodrug conversion or induction of tumor cell apoptosis). MSCs as a crucial segment of the tumor surroundings and their confirmed tumor tropism, are assumed to be an open gateway for the design of promising drug delivery systems. The presented paper reviews current publications in this fieldwork, searches out the most recent patents that were published after 2012 (WO2014066122, US20140017787, WO2015100268, US20150086515), and tries to present the current progress and future prospective on the design and development in anti-cancer drug delivery systems based on MSCs.

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“…The stem cells are being tested for their potential for carrying the suicidal genes also into variety of other tumors [135][136][137][138][139][140][141][142][143][144][145][146][147][148].…”

Section: Vectors Of Suicidal Genesmentioning

confidence: 99%

“…HSV-TK is effectively used in cancer suicide gene therapy by expression in targeted cells to exert intracellular effects outlined above [15][16][17][18][19][22][23][24]. Alternatively, TK is also secreted into the extracellular fluids by genetically engineered cells [135][136][137][138][139][140][141][142][143][144][145][146][147][148]. Thereafter, it is internalized by surrounding cancer cells to cause their death.…”

Section: Mechanisms Of Inducing Cancer Cells' Deathmentioning

confidence: 99%

Frontiers in Suicide Gene Therapy of Cancer

Malecki¹

2012

J Genet Syndr Gene Ther

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The National Cancer Institute (NCI) and the American Cancer Society (ACS) predict that 1,638,910 men and women will be diagnosed with cancer in the USA in 2012. Nearly 577,190 patients will die of cancer of all sites this year. Patients undergoing current systemic therapies will suffer multiple side effects from nausea to infertility. Potential parents, when diagnosed with cancer, will have to deposit oocytes and sperms prior to starting systemic radiation or chemo-therapy for the future genetic testing and in vitro fertilization, while trying to avoid risks of iatrogenic mutations in their germ cells. Otherwise, children of parents treated with systemic therapies, will be at high risk of developing genetic disorders. According to these predictions, this year will carry another, very poor therapeutic record again.The ultimate goal of cancer therapy is the complete elimination of all cancer cells, while leaving all healthy cells unharmed. One of the most promising therapeutic strategies in this regard is cancer suicide gene therapy (CSGT), which is rapidly progressing into new frontiers.The therapeutic success, in CSGT, is primarily contingent upon precision in delivery of the therapeutic transgenes to the cancer cells only. This is addressed by discovering and targeting unique or / and over-expressed biomarkers displayed on the cancer cells and cancer stem cells. Specificity of cancer therapeutic effects is further enhanced by designing the DNA constructs, which put the therapeutic genes under the control of the cancer cell specific promoters. The delivery of the suicidal genes to the cancer cells involves viral, as well as synthetic vectors, which are guided by cancer specific antibodies and ligands. The delivery options also include engineered stem cells with tropisms towards cancers. Main mechanisms inducing the cancer cells' deaths include: transgenic expression of thymidine kinases, cytosine deaminases, intracellular antibodies, telomeraseses, caspases, DNases. Precautions are undertaken to eliminate the risks associated with transgenesis.Progress in genomics and proteomics should help us in identifying the cancer specific biomarkers and metabolic pathways for developing new strategies towards clinical trials of targeted and personalized gene therapy of cancer.

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HSV-tk expressing mesenchymal stem cells exert bystander effect on human glioblastoma cells

Cited by 155 publications

References 27 publications

A designed equine herpes thymidine kinase (EHV4 TK) variant improves ganciclovir-induced cell-killing

A designed equine herpes thymidine kinase (EHV4 TK) variant improves ganciclovir-induced cell-killing

Perspectives in Engineered Mesenchymal Stem/Stromal Cells Based Anti- Cancer Drug Delivery Systems

Frontiers in Suicide Gene Therapy of Cancer

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