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Isolation of Exosome-Enriched Extracellular Vesicles Carrying Granulocyte-Macrophage Colony-Stimulating Factor from Embryonic Stem Cells
Published on: November 11, 2021
Stem cells-derived suicide gene exosomes: a promising platform for innovative cancer therapy
Dajana Vanova1,2, Michal Andrezal2, Ursula Altanerova2
1Cancer Research Institute, Biomedical Research Center of the Slovak Academy of Sciences, Bratislava, Slovakia.
Abstract:
Innovative cancer treatments are needed for metastatic tumors that currently do not have adequate therapies. This review highlights recent progress in suicide gene therapy using small extracellular vesicles, particularly exosomes, as a novel form of intracellular anticancer therapy. Suicide gene exosomes are produced by tumor-targeting human mesenchymal stem cells (MSC) that have been genetically modified to express the yeast cytosine deaminase::uracil phosphoribosyl transferase fused gene (yCD::UPRT) along with the prodrug 5-fluorocytosine (5-FC). The yCD::UPRT-MSC-secretome containing tumor-targeted exosomes converts 5-FC into the cytotoxic compound 5-fluorouracil (5-FU) and its metabolites within the tumor environment. The second popular system we are investigating involves the suicide gene exosomes derived from thymidine kinase of Herpes Simplex Virus in conjunction with a prodrug ganciclovir. Extracellular vesicles secreted by tumor-associated cells contribute to tumor growth and metastasis. When these cells are transduced with yCD::UPRT suicide gene, they can act as a source of therapeutic exosomes capable of intracellularly converting nontoxic prodrug 5-FC to a cytotoxic 5-FU. Combined action of suicide gene exosomes from MSCs and cancer-associated fibroblasts is a promising platform for aggressive tumor treatment. Furthermore, suicide gene exosomes can be enhanced with additional anticancer drugs and customized for targeted delivery. In this review, we trace the history of these findings, present therapeutic outcomes from in vitro and in vivo studies, and explore the future potential of therapeutically beneficial exosomes for cancer treatment.
Insights
Suicide gene exosomes, engineered from modified stem cells, offer a novel cancer therapy. These exosomes deliver therapeutic genes to tumors, converting prodrugs into cancer-killing agents for improved treatment outcomes.
Area of Science:
- Oncology
- Biotechnology
- Nanomedicine
Background:
- Metastatic tumors often lack effective treatment options.
- Small extracellular vesicles, particularly exosomes, are emerging as novel drug delivery vehicles.
- Current cancer therapies require innovative approaches for improved efficacy.
Purpose of the Study:
- To review recent advancements in suicide gene exosome therapy for cancer.
- To explore the potential of engineered exosomes as intracellular anti-cancer drugs.
- To highlight therapeutic outcomes and future directions for exosome-based cancer treatments.
Main Methods:
- Production of suicide gene exosomes from genetically modified human mesenchymal stem cells (MSCs) expressing yeast cytosine deaminase::uracil phosphoribosyl transferase (yCD::UPRT).
- Utilizing tumor-targeting exosomes to convert the prodrug 5-fluorocytosine (5-FC) into the cytotoxic compound 5-fluorouracil (5-FU) within the tumor microenvironment.
- Investigating suicide gene exosomes derived from Herpes Simplex Virus thymidine kinase and ganciclovir.
Main Results:
- Engineered exosomes effectively convert prodrugs into cytotoxic agents specifically within tumor cells.
- Combined therapy using suicide gene exosomes from MSCs and cancer-associated fibroblasts (CAFs) shows promise for aggressive tumors.
- In vitro and in vivo studies demonstrate therapeutic potential of suicide gene exosomes.
Conclusions:
- Suicide gene exosomes represent a promising platform for intracellular anti-cancer drug delivery.
- Exosome-based therapies can be enhanced with additional drugs and customized for targeted delivery.
- Further research into therapeutically beneficial exosomes holds significant potential for future cancer treatment strategies.
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