Cytosine deaminase expressing human mesenchymal stem cells mediated tumour regression in melanoma bearing mice

Kučerová, Lucia; Matúšková, Miroslava; Pastorakova, Andrea; Tyciakova, Silvia; Jakubíková, Jana; Bohovic, Roman; Altanerová, Veronika; Altaner, Č

doi:10.1002/jgm.1239

Cited by 162 publications

(139 citation statements)

References 42 publications

Supporting

Mentioning

133

Contrasting

Unclassified

Order By: Relevance

“…Although many groups are improving the delivery vectors [adenovirus (3), retrovirus and cell carriers (22)] and bystander effect of suicide genes (23) to increase their therapeutic effect, the results of clinical trials indicate a need for greater efficacy (24).…”

Section: Discussionmentioning

confidence: 99%

Positive selection of gene-modified cells increases the efficacy of pancreatic cancer suicide gene therapy

Martínez-Quintanilla

Cascalló

Gros

et al. 2009

Molecular Cancer Therapeutics

View full text Add to dashboard Cite

Thymidine kinase (TK)-mediated suicide gene therapy has been considered for the treatment of pancreatic cancer. However, despite a bystander effect, the proportion of transduced tumor cells has proven too low to result in efficacy. We propose the use of a drug-selectable marker (MDR1) to enrich TK-expressing cells using chemotherapy. This enrichment or positive selection phase may increase the efficacy of suicide gene therapy. To test this strategy, we generated stable NP18MDR/TK-GFP transfectants and showed docetaxel resistance in vivo. Mixed tumors of MDR/TK-expressing cells and parental NP18 cells were established and docetaxel was used to increase the proportion of TK-expressing cells. After this positive selection phase, suicide gene therapy with ganciclovir was applied. Upon positive selection, the proportion of TK-expressing cells increased from 4% to 22%. Subsequent suicide gene therapy was more effective compared with a control group without positive selection. Starting with 10% of TK-expressing cells the positive-negative selection strategy completely inhibited tumor growth. Taken together, these results suggest that a positive-negative selection strategy based on MDR and TK genes represents an efficient way to increase the proportion of TKexpressing cells in the tumor and the efficacy of TKmediated suicide gene therapy.

show abstract

Section: Discussionmentioning

confidence: 99%

Positive selection of gene-modified cells increases the efficacy of pancreatic cancer suicide gene therapy

Martínez-Quintanilla

Cascalló

Gros

et al. 2009

Molecular Cancer Therapeutics

View full text Add to dashboard Cite

show abstract

“…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

View full text Add to dashboard Cite

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.

show abstract

“…Active drugs are able to attack neighboring cancer cells via the gap junction, intracellular communication, and connexins; this process is known as bystander effect (Kandouz and Batist, 2010). MSCs-based gene therapy has been used to treat several diseases in animal models including glioblastoma (Altaner et al, 2014;Altanerova et al, 2012;Fei et al, 2012;Lee et al, 2009), prostate cancer (Cavarretta et al, 2010), melanoma (Kucerova et al, 2008), gastrointestinal cancer (You et al, 2009), and other malignancies. Along with MSCs, neural stem cells (NSCs) carrying suicide enzyme have shown to reduce tumor volume and to increase survival in mouse model of malignant disease including medulloblastoma (Kim et al, 2006), melanoma brain metastases (Aboody et al, 2006), glioblastoma (Barresi et al, 2003;Ito et al, 2010), breast cancer brain metastases (Joo et al, 2009), prostate cancer , and breast cancer (Yi et al, 2014).…”

Section: Stem Cells As Vectors Carrying Therapeutic Reagents To Tumorsmentioning

confidence: 99%

Stem cell technology and engineering for cancer treatment

Truong

Pham

2015

Biomed Res Ther

View full text Add to dashboard Cite

Abstract-Stem cells are not only widely used for regenerative medicine, but are also considered as a useful tool for cancer treatment. For a long time, stem cells have been utilized to renew the immune system for radiation or chemotherapy treated patients. Recently, stem cells are being engineered to carry therapeutic reagents to target tumor sites. Cancer vaccines based on the knowledge of cancer stem cells have been studied and applied for cancer treatment. Induced pluripotent stem cells have been used to create active T cells to support cancer immunotherapy. Those are due to the unique characteristics of stem cells, such as immunological tolerance, migration, and tissue reparation. This review discusses stem cell applications in transplantation, stem cell-based carriers, induced-pluripotent stem cells, cancer stem cells, and potential of stem cells engineering to revolutionize cancer treatment.

show abstract

Cytosine deaminase expressing human mesenchymal stem cells mediated tumour regression in melanoma bearing mice

Cited by 162 publications

References 42 publications

Positive selection of gene-modified cells increases the efficacy of pancreatic cancer suicide gene therapy

Positive selection of gene-modified cells increases the efficacy of pancreatic cancer suicide gene therapy

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

Stem cell technology and engineering for cancer treatment

Contact Info

Product

Resources

About