Abstract
Background: Tumors, including NSCLC, develope numerous local mechanisms which impair maturation of dendritic cells (DCs). The delivery of stimulatory signals to DCs in cancer microenvironment is believed to be an effective means to break tumor-induced tolerance.
Aim: Evaluation of immunostimulatory properties of TLR5 ligand, FliC, cell membrane-displayed in experimental model of Lewis Lung Cancer (LLC) transfected with a novel plasmid vector system.
Methods: Cell membrane-expressed humanized FliC transgene was inserted to the pCDNA3.1Zeo(+) plasmid-based construct. Tumor specific two-step transcriptional activation system was additionally used. A549 cells, the model of NSCLC, transfected with FliC-coding plasmid, induced the maturation of human monocyte-derived DCs in co-cultures. Two groups of C57BL6 mice bearing a subcutaneous LLC tumor were injected intratumoraly with in vivo-JetPEI and FliC plasmids or in vivo-JetPEI and phosphate-buffered saline as a control. Four administrations were performed within 1 week. Tumor volumes and animal survival were monitored for 6 weeks.
Results: Plasmid injections delayed the growth of implanted LLC tumors and significantly improved animal survival rates. Histological examination of specific plasmid-injected tumors revealed lymphocyte infiltrates and remarkable necrosis.
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