Mesenchymal stem cell delivery of TRAIL can eliminate metastatic cancer

Area of Science:

• Oncology
• Stem Cell Therapy
• Gene Therapy

Background:

• Cancer remains a leading global cause of death, necessitating novel therapeutic strategies.
• Mesenchymal stem cells (MSCs) demonstrate tumor-homing capabilities and can be engineered for targeted delivery.
• Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces selective apoptosis in various cancer cells.

Purpose of the Study:

• To investigate the efficacy of MSCs engineered to express tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) for cancer treatment.
• To evaluate the tumor-homing and cancer cell-killing potential of these engineered MSCs in preclinical models.

Main Methods:

• Human MSCs were genetically modified using lentiviral vectors to express TRAIL under a tetracycline-inducible promoter.
• In vitro studies involved co-culturing engineered MSCs with various cancer cell lines (A549, MDAMB231, H357, Hela).
• In vivo studies utilized subcutaneous xenografts and a pulmonary metastasis model in mice.

Main Results:

• Engineered MSCs induced apoptosis and death in multiple cancer cell lines in vitro.
• Directly delivered TRAIL-expressing MSCs significantly reduced tumor growth in subcutaneous xenografts.
• Systemically delivered MSCs localized to lung metastases, and controlled TRAIL delivery led to complete clearance of metastatic disease in 38% of mice.

Conclusions:

• Inducible TRAIL-expressing MSCs represent a promising therapeutic approach for reducing metastatic tumor burden.
• This strategy demonstrated frequent eradication of metastases, highlighting its potential in cancer treatment.
• Engineered MSCs offer a potential adjuvant therapy for clearing micrometastatic disease post-resection.