Non-viral delivery of interleukin-2 and soluble Flk-1 inhibits metastatic and primary tumor growth in renal cell carcinoma

摘要: Treatments for renal cell carcinoma, while promising, are still limited by toxicity and cost. In the hopes of finding a novel compound or combination, we developed plasmid containing genes interleukin-2 (IL-2) soluble vascular endothelial growth factor receptor 2 (msFlk1). The plasmid, p2CMVIL2/msFlk1, demonstrated similar in vitro transgene expression IL-2 msFlk1 compared to their single-agent counterparts. Subcutaneous tumor was significantly inhibited p2CMVIL2/msFlk1 group when delivered locally non-viral water polymer, WSLP exhibited 50% increase survival over glucose controls. vivo experimentation that WSLP/msFlk1 decreased microvessel density pCMVmsFlk1 treated groups. Furthermore, tumor-infiltrating lymphocytes expressing CD45RO CD68 were increased within microenvironment upon treatment. To determine effects an experimental RENCA lung metastases model, therapeutic DNA systemically following complexation with angiogenic endothelial-targeting polymer PEI-g-PEG-RGD. treatment reduced 56% therapy proportions all Our work clearly demonstrates delivery can inhibit synergistic manner may represent new carcinoma.