A long-lasting dendritic cell DNA vaccination system using lysinylated amphiphiles with mannose-mimicking head-groups.
Dendritic cells (DCs) pulsed/transduced with tumor-associated or viral antigens have shown promise in combating cancer and infectious diseases. Despite significant progresses, development of a biologically safe DC-based genetic immunization (DNA vaccination) system capable of providing truly long-lasting protective immunity remains a significant scientific challenge. Here we show that immunization with autologous DCs pre-transfected with electrostatic complexes (lipoplexes) of a plasmid DNA encoding melanoma tumor associated antigen and liposomes of two lysinylated cationic amphiphiles with mannose-mimicking quinic and shikimic acid head-groups provides long-lasting (300 days post tumor challenge) protective immunity with significant memory response (more than six months after the second tumor challenge) in more than 80% immunized mice. The presently described non-viral ex vivo DC-transfection system may be exploited in inducing long-lasting immune response in DC-based genetic immunization.
Division of Lipid Science and Technology, Indian Institute of Chemical Technology, Hyderabad 500 007, India.
Ramishetti
R
Srinivas
Arup
A
Garu
Gopikrishna
G
Moku
Sachin B
SB
Agawane
Arabinda
A
Chaudhuri
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D005434:Flow Cytometry; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008297:Male; D008358:Mannose / Q000737:chemistry*; D008545:Melanoma / Q000276:immunology* / Q000378:metabolism / Q000517:prevention & control; D051379:Mice; D008810:Mice, Inbred C57BL; D014162:Transfection / Q000379:methods*; D019444:Vaccines, DNA / Q000737:chemistry* / Q000627:therapeutic use*
D019444:Vaccines, DNA; D015847:Interleukin-4; D007371:Interferon-gamma; D008358:Mannose