Continuous release of endostatin from microencapsulated engineered cells for tumor therapy

Research studies suggest that tumor-related angiogenesis contributes to the phenotype of malignant gliomas. We assessed the effect of local delivery o f the angiogenesis inhibitor endostatin on human glioma cell line (U-87MG) xenografts. Baby hamster kidney (BHK) cells were stably transfected with a human endostatin (hES) expression vector and were encapsulated in alginate- poly L-lysine (PLL) microcapsules for long-term delivery of hES. The releas e of biologically active endostatin was confirmed using assays of bovine ca pillary endothelial (BCE) proliferation and of tube formation. Human endost atin released from the microcapsules brought about a 67.2% inhibition of BC E proliferation. Furthermore, secreted hES was able to inhibit tube formati on in KDR/PAE cells (porcine aortic endothelial cells stably transfected wi th KDR, a tyrosine kinase) treated with conditioned U-87MG medium. A single local injection of encapsulated endostatin-secreting cells in a nude mouse model resulted in a 72.3% reduction in subcutaneous U87 xenografts' weight 21 days post treatment. This inhibition was achieved by only 150.8 ng/ml h uman endostatin secreted from 2 x 10(5) encapsulated cells. Encapsulated en dostatin-secreting cells are effective for the treatment of human glioblast oma xenografts. Continuous local delivery of endostatin may offer an effect ive therapeutic approach to the treatment of a variety of tumor types.