Prodrug Gene Therapy for Cancer Mediated by Mesenchymal Stem/Stromal Cells Engineered to Express Yeast Cytosinedeaminase::Uracilphos phoribosyltransferaseCestmir Altaner1,2*
- *Corresponding Author:
- Cestmir Altaner
Cancer Research Institute
Slovak Academy of Sciences
Tel: (+421 2) 59327 426
Fax: (+421 2)59327 409
E-mail: [email protected]
Received date: December 31, 2014; Accepted date: February 05, 2015; Published date: February 07, 2015
Citation: Altaner C (2015) Prodrug Gene Therapy for Cancer Mediated by Mesenchymal Stem/Stromal Cells Engineered to Express Yeast Cytosined eaminase::Uracilphosphoribosyltransferase. J Stem Cell Res Ther 5:264. doi:10.4172/2157-7633.1000264
Copyright: © 2015 Altaner C, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Prodrug cancer gene therapy mediated by human adipose tissue-derived mesenchymal stem/stromal cells (MSCs) engineered to express fused yeast cytosine deaminase::uracil phosphoribosyltransferase (Therapeutic Stem/Stromal Cells-ThSC) is an efficient experimental therapeutic modality for cancers. The attractiveness of prodrug cancer gene therapy by stem/stromal cells targeted to tumors lies in activating the nontoxic prodrug 5-fluorocytosine directly within the tumor mass to 5-fluorouracil, thus avoiding systemic toxicity. Prodrug administration not only eliminates tumor cells, but consequently kills the more resistant ThSC as well. The therapeutic potential of this system is universal and quite effective. In a series of papers, it was shown its effectiveness in targeting and killing human colorectal, melanoma, glioblastoma, colon, breast and bladder carcinoma cells both in vitro, and in vivo. Pilot preclinical studies demonstrated that intravenously administered ThSC were effective in significantly inhibiting subcutaneous xenografts bone metastatic prostate cells. Similar inhibiting effects were seen on spontaneous aggressive prostate adenocarcinoma on TRAMP mice. Complete tumor regression was observed in a rat glioblastoma intracerebral model. It is assumed that curative glioblastoma therapy is a consequence of elimination of glioma stem cells that drive the tumor progression. Both vector composition and unique properties of the vehicle stem/stromal cells contribute to high therapeutic efficiency. Mesenchymal stem/stromal cells transduced stably with yCD::UPRT gene produced exosomes. The exosomes upon easy internalization to tumor cells in the presence of 5-FC inhibit growth of a broad kind of cancer cells in vitro. The exosomes released from therapeutic stem/stromal cells significantly contribute to the therapeutic efficiency of the yCD::UPRT-MSCs/5-FC system. Results support arguments for beginning clinical studies for the treatment of high grade tumors and metastases.