Interactions and mechanisms of bystander effect mediated by mesenchymal stromal cells expressing prodrug-converting genes on tumour stem cells

Project leader: Miroslava Matúšková
Project duration: 2013 - 2017

The project is based on targeted cancer gene therapy mediated by adipose tissue-derived mesenchymal stromal cells (AT-MSC) expressing prodrug –converting genes. Mesenchymal stromal cells (MSC) represent a unique combination of gene and cell therapy. Thanks to their natural affinity to tumour tissue these cells are able to home into the tumour after systemic administration, and thus deliver the therapeutic molecule to the target place. MSC expressing prodrug-converting genes seem to be a new therapeutic approach in metastases and other issues which cannot be cured by surgery or radiotherapy. Metastatic dissemination and relapse of the disease is caused by tumour initiating cells (cancer stem cells) which are characterized by increased resistance. The efficacy of treatment by genetically engineered MSC on cancer stem cells has not been demonstrated yet. We will isolate subpopulations with cancer stem cells’ properties from cell lines derived from melanoma or colorectal adenocarcinoma. WE aim: (i.) to find out the efficacy of gene therapy mediated by MSC expressing yeast cytosine deaminase (simple one or fused with phosphoribosyltransferase) or Herpes simplex virus thymidine kinase on cancer stem cells and; (ii.) define interactions between MSC and tumour-initiating cells.


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