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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Acknowledgements
We thank the Quality Control Department, Cobra Therapeutics, for endotoxin testing of plasmid DNA samples, the Manchester Blood Transfusion Service for supplying buffy coats, blood donors at Cobra Therapeutics and the Institute of Cancer Studies, Birmingham University, Yalem Bekele for phlebotomy and plasmid DNA preparation, Dr. T. Hanke for the influenza nucleoprotein gene, and the Bioconjugate Chemistry Department at Cobra Therapeutics for peptide synthesis.
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Irvine, A., Trinder, P., Laughton, D. et al. Efficient nonviral transfection of dendritic cells and their use for in vivo immunization. Nat Biotechnol 18, 1273–1278 (2000). https://doi.org/10.1038/82383
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DOI: https://doi.org/10.1038/82383
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