Nature Biotechnology
18, 1273 - 1278 (2000)
doi:10.1038/82383
Efficient nonviral transfection of dendritic cells and their use for
in vivo immunizationAlistair S. Irvine1, Peter K.E. Trinder1, David L. Laughton1, 3, Helen Ketteringham1, Ruth H. McDermott1, 4, Sophie C.H. Reid1, Adrian M.R. Haines1, Abdu Amir1, Rhonda Husain1, Rajeev Doshi1, Lawrence S. Young2
& Andrew Mountain11
Cobra Therapeutics, The Science Park, University of
Keele, Keele, Staffordshire ST5 5SP,
United Kingdom. 2
CRC Institute of Cancer Studies, University of Birmingham, Birmingham B15 2TA, United Kingdom. 3
Present address: Lead Generation Biology, AstraZeneca
R&D Charnwood, Loughborough, Leicestershire,
LE11 5RH, United Kingdom. 4
Present address: Manchester Innovation Ltd.,
Incubator Building, Grafton Street, Manchester M13 9XX,
United Kingdom.
Correspondence should be addressed to Andrew Mountain andy.mountain@cobrat.comNonviral transfectiondendritic cellscancer immunotherapygenetic modificationImmunization 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.
|
