Efficient nonviral transfection of dendritic cells and their use for in vivo immunization |
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Authors: | Irvine A S Trinder P K Laughton D L Ketteringham H McDermott R H Reid S C Haines A M Amir A Husain R Doshi R Young L S Mountain A |
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Affiliation: | Cobra Therapeutics, The Science Park, University of Keele, Keele, Staffordshire ST5 5SP, United Kingdom. |
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Abstract: | Immunization with dendritic cells (DCs) transfected with genes encoding tumor-associated antigens (TAAs) is a highly promising approach to cancer immunotherapy. We have developed a system, using complexes of plasmid DNA expression constructs with the cationic peptide CL22, that transfects human monocyte-derived DCs much more efficiently than alternative nonviral agents. After CL22 transfection, DCs expressing antigens stimulated autologous T cells in vitro and elicited primary immune responses in syngeneic mice, in an antigen-specific manner. Injection of CL22-transfected DCs expressing a TAA, but not DCs pulsed with a TAA-derived peptide, protected mice from lethal challenge with tumor cells in an aggressive model of melanoma. The CL22 system is a fast and efficient alternative to viral vectors for engineering DCs for use in immunotherapy and research. |
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