Efficient nonviral transfection of dendritic cells and their use for in vivo immunization.
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.
Irvine
A S
AS
Cobra Therapeutics, The Science Park, University of Keele, Keele, Staffordshire ST5 5SP, United Kingdom.
Trinder
P K
PK
Laughton
D L
DL
Ketteringham
H
H
McDermott
R H
RH
Reid
S C
SC
Haines
A M
AM
Amir
A
A
Husain
R
R
Doshi
R
R
Young
L S
LS
Mountain
A
A
D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000276:immunology; D002412:Cations; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins; D006801:Humans; D007114:Immunization; D007167:Immunotherapy; D019746:Intramolecular Oxidoreductases / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008546:Melanoma, Experimental / Q000276:immunology / Q000628:therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D010455:Peptides / Q000737:chemistry / Q000235:genetics; D010957:Plasmids / Q000235:genetics; D014162:Transfection; D014407:Tumor Cells, Cultured
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D002412:Cations; D008164:Luminescent Proteins; D010455:Peptides; D049452:Green Fluorescent Proteins; D019746:Intramolecular Oxidoreductases; C042501:dopachrome isomerase