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Published on: February 21, 2025
Stem cell based cancer gene therapy
Marina Cihova1, Veronika Altanerova, Cestmir Altaner
1Cancer Research Institute, Slovak Academy of Sciences, Bratislava, Slovakia.
Abstract:
The attractiveness of prodrug cancer gene therapy by stem cells targeted to tumors lies in activating the prodrug directly within the tumor mass, thus avoiding systemic toxicity. Suicide gene therapy using genetically engineered mesenchymal stem cells has the advantage of being safe, because prodrug administration not only eliminates tumor cells but consequently kills the more resistant therapeutic stem cells as well. This review provides an explanation of the stem cell-targeted prodrug cancer gene therapy principle, with focus on the choice of prodrug, properties of bone marrow and adipose tissue-derived mesenchymal stem and neural stem cells as well as the mechanisms of their tumor homing ability. Therapeutic achievements of the cytosine deaminase/5-fluorocytosine prodrug system and Herpes simplex virus thymidine kinase/ganciclovir are discussed. In addition, delivery of immunostimulatory cytokines, apoptosis inducing genes, nanoparticles and antiangiogenic proteins by stem cells to tumors and metastases is discussed as a promising approach for antitumor therapy. Combinations of traditional, targeted and stem cell-directed gene therapy could significantly advance the treatment of cancer.
Insights
Stem cell-targeted prodrug cancer gene therapy activates treatments directly in tumors, reducing toxicity. This approach, using engineered stem cells, offers a safer suicide gene therapy by eliminating both tumor and resistant stem cells.
Area of Science:
- Oncology
- Gene Therapy
- Stem Cell Biology
Background:
- Prodrug cancer gene therapy aims to activate therapeutic agents within tumor masses to minimize systemic toxicity.
- Suicide gene therapy using genetically engineered mesenchymal stem cells offers a safety advantage by eliminating both tumor cells and resistant therapeutic stem cells post-prodrug administration.
Purpose of the Study:
- To explain the principles of stem cell-targeted prodrug cancer gene therapy.
- To review key components including prodrug selection, stem cell properties (mesenchymal and neural), and tumor homing mechanisms.
- To discuss therapeutic achievements and future directions in stem cell-mediated antitumor strategies.
Main Methods:
- Review of existing literature on stem cell-targeted prodrug cancer gene therapy.
- Focus on mesenchymal stem cells (bone marrow and adipose-derived) and neural stem cells.
- Analysis of specific prodrug systems (cytosine deaminase/5-fluorocytosine and HSVtk/ganciclovir) and their therapeutic outcomes.
Main Results:
- Stem cell-targeted therapy enables localized prodrug activation, enhancing efficacy and reducing side effects.
- Mesenchymal and neural stem cells demonstrate tumor-homing capabilities suitable for targeted delivery.
- Successful therapeutic outcomes have been reported for specific prodrug systems, with potential for broader applications.
Conclusions:
- Stem cell-targeted prodrug gene therapy presents a promising strategy for localized cancer treatment with improved safety profiles.
- The delivery of various therapeutic payloads, including cytokines, apoptosis-inducing genes, and nanoparticles, via stem cells offers versatile antitumor approaches.
- Combining conventional, targeted, and stem cell-directed gene therapies holds significant potential for advancing cancer treatment modalities.
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