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

Introduction: Cancer immunotherapy emerged as a novel therapeutic option making use of enhanced or amended native immune system to create a robust response against malignant cells. Cancer vaccines, monoclonal antibodies (mAbs), cell therapy and non-specific cancer immunotherapies with adjuvants are all produced encouraging results either as prescribed drug or at clinical trial phase or as an active research field. 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 remarkable reduction of systemic side effects.Description: 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 vascular leak, hypotension and respiratory insufficiency. Natural and strong tropism of MSCs towards malignant cells made them an ideal systemic delivery vehicle to direct the proposed therapeutic genes to the vicinity of a tumor where its expression could evoke an immune reaction against the tumor. Compared with other methods, the delivery of cytokines via engineered MSCs is a more practical, safe, and promising strategy. Large numbers of genes code for cytokines have been utilized to reengineer MSCs as therapeutic cells. This review highlights the recent literature on cytokine gene therapy to confront human malignancies with focused on MSCs application in cancer immunotherapy.Conclusion: Taken together, these studies introduce engineered MSCs as a new research field for cancer treatment. Their utilization will be of great benefit to future cancer patients.

کلیدواژه ها:

Mesenchymal stem cells ، immunotherapy ، cancer ، cytokine