Generation of potent and specific cellular immune responses via in vivo stimulation of dendritic cells by pNGVL3-hFLex plasmid DNA and immunogenic peptides.
Dendritic cells (DC) are the most potent professional antigen-presenting cells with exquisite capacity to interact with T cells to initiate strong primary cellular immune responses. The antigen-presenting capability of DC makes them attractive vehicles for the delivery of therapeutic cancer vaccines. Recently, we have demonstrated that the introduction of a recombinant gene encoding the human Flt3L gene into mice could result in the expansion of the DC population in vivo. In this report, we have introduced the human Flt-3L gene via naked DNA-based immunization in combination with the muc-1 tumor peptide to immunize mice. We demonstrated that the population of DC expanded following stimulation with the human Flt-3L gene in vivo is functional and they are able to elicit potent muc-1 peptide-specific cellular responses. The strategy described here allows the efficient generation of antigen-specific CTL immunity in vivo and has the potential to be applied in developing efficient protocols for antigen-specific immunotherapy of human malignancies.
Fong
C L
CL
Gene Vector Laboratory, Division of Cellular and Molecular Research, National Cancer Center, Singapore.
Hui
K M
KM
D000818:Animals; D001854:Bone Marrow Cells; D019496:Cancer Vaccines / Q000008:administration & dosage*; D002455:Cell Division; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D006801:Humans; D007167:Immunotherapy; D008213:Lymphocyte Activation; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D018396:Mucin-1 / Q000235:genetics; D010446:Peptide Fragments / Q000235:genetics; D013154:Spleen / Q000166:cytology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D019496:Cancer Vaccines; C116055:MUC1 tandem repeat peptide; D008565:Membrane Proteins; D018396:Mucin-1; D010446:Peptide Fragments; C084881:flt3 ligand protein