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Genetically engineered mesenchymal stem cells: targeted delivery of immunomodulatory agents for tumor eradication

Cancer Gene Therapy volume 27, pages 854–868 (2020)Cite this article

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Abstract

Cancer immunotherapy emerged as a novel therapeutic option that employs enhanced or amended native immune system to create a robust response against malignant cells. The systemic therapies with immune-stimulating cytokines have resulted in substantial dose-limiting toxicities. Targeted cytokine immunotherapy is being explored to overcome the heterogeneity of malignant cells and tumor cell defense with a remarkable reduction of systemic side effects. Cell-based strategies, such as dendritic cells (DCs), fibroblasts or mesenchymal stem cells (MSCs) seek to minimize the numerous toxic side effects of systemic administration of cytokines for extended periods of time. The usual toxicities comprised of a vascular leak, hypotension, and respiratory insufficiency. Natural and strong tropism of MSCs toward malignant cells made them an ideal systemic delivery vehicle to direct the proposed therapeutic genes to the vicinity of a tumor where their expression could evoke an immune reaction against the tumor. Compared with other methods, the delivery of cytokines via engineered MSCs is safer and renders a more practical, and promising strategy. Large numbers of genes code for cytokines have been utilized to reengineer MSCs as therapeutic cells. This review highlights the recent findings on the cytokine gene therapy for human malignancies by focusing on MSCs application in cancer immunotherapy.

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Fig. 1: Potential of MSCs in targeted cancer therapy.

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  1. These authors contributed equally: Meysam Mosallaei, Miganoosh Simonian

Authors and Affiliations

  1. Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

    Meysam Mosallaei, Naeim Ehtesham, Nasim Vatandoost & Rasoul Salehi

  2. Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran

    Miganoosh Simonian & Babak Negahdari

  3. Department of Medical Genetics, School of Medicine, Bam University of Medical Sciences, Bam, Iran

    Mohammad Reza Karimzadeh

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Mosallaei, M., Simonian, M., Ehtesham, N. et al. Genetically engineered mesenchymal stem cells: targeted delivery of immunomodulatory agents for tumor eradication. Cancer Gene Ther 27, 854–868 (2020). https://doi.org/10.1038/s41417-020-0179-6

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