Bioengineer mesenchymal stem cell for Treatment of glioma by IL-12 mediated microenvironment reprogramming and nCD47-SLAMF7 mediated phagocytosis regulation of macrophages

High expression of cellular self-activated immunosuppressive molecules and extensive infiltration of suppressive immune cells in the tumor microenvironment are the main factors leading to the resistance of glioma to immunotherapy. However, the technology related to modifying the expression of glioma cellular self-molecules based on gene editing still needs to be developed. In this project, cell therapy strategies were developed to reverse the immunosuppressive microenvironment of glioma (TIME). Mesenchymal stem cells (MSCs) derived from bone marrow were used as carriers to express bioactive proteins, which could exhibit tumor-homing characteristics in response to tumor TGF-β signals. MSCs were modified to express the secretory anti-tumor immune cytokine IL-12 and the nCD47-SLAMF7 fusion protein, which regulates the phagocytosis of macrophages. The engineered MSCs are then injected in situ into the area near the glioma to bypass the blood-brain barrier and provide localized high concentrations of bioactive proteins. This approach could significantly activate natural and adaptive immune cells in the TIME, ultimately leading to the effective control of glioma. This study provides a new strategy for the clinical treatment of glioma patients and the prevention of postoperative recurrence.