A Tumor-selective Biotherapy With Prolonged Impact on Established Metastases Based on Cytokine Gene-engineered MSCs

摘要: The poor prognosis for patients with advanced malignancy relates partly to the inability reverse cancer metastasis. In this study we have investigated an integrated immunotherapy method against pre-established metastases in three kinds of models including B16 melanoma, 4T1 breast tumor, and Hca hepatoma. progression into multistep lymph nodes (LN) internal organs was, markedly impeded midway stage reversed ultimate following a 20-day course intravenous [with interleukin-12 (IL-12) gene-engineered mesenchymal stem cells (MSCs), administered once every 5 days P < 0.05)]; therapy was without systemic toxic effects. As control, obvious toxicity observed free AdIL-12 group, yet metastasis delayed only but not stage. Enzyme-linked immunosorbent assay (ELISA) showed that intratumoral expression levels IL-12 were enhanced by cytokine-engineered MSCs be tenfold greater than groups stage; conversely, elevated serum, IL-12, during Furthermore, histomorphometric analysis revealed reductive tendency toward reversion tumor-associated lymphatic sprouts increased tumor apoptosis index engineered MSC (P 0.05). These data indicate potential considered as therapeutic weapon targeting malignancies.