Plasmid DNA encoding human carcinoembryonic antigen (CEA) adsorbed onto cationic microparticles induces protective immunity against colon cancer in CEA-transgenic mice.
A carcinoembryonic antigen (CEA)-based DNA vaccine, adsorbed onto cationic microparticles of poly(DL-lactide-co-glycolide) (PLG) induced tumor-protective immunity against a lethal challenge of MC38-CEA colon carcinoma cells in CEA-transgenic mice that was more potent than that of the corresponding naked DNA vaccine. Boosting with a plasmid encoding murine GM-CSF increased the vaccine's efficacy leading to a complete rejection of tumor cells in 50% of mice. This effect was due to activation of MHC class I-restricted CD8(+) T cells coupled with an increased secretion of proinflammatory cytokines IFN-gamma, TNF-alpha and IL-2. Also, specific activation of dendritic cells was indicated by a two-three-fold upregulation of their costimulatory CD80 and MHC class II molecules. This approach may be a promising new strategy for the rational design of cancer vaccines for future clinical applications.
Luo
Yunping
Y
Department of Immunology, The Scripps Research Institute, 10550 North Torrey Pines Road, IMM13, La Jolla, CA 92037, USA.
O'Hagan
Derek
D
Zhou
He
H
Singh
Manmohan
M
Ulmer
Jeffrey
J
Reisfeld
Ralph A
RA
James Primus
F
F
Xiang
Rong
R
D000230:Adenocarcinoma / Q000276:immunology* / Q000517:prevention & control; D000818:Animals; D002272:Carcinoembryonic Antigen / Q000235:genetics* / Q000276:immunology*; D003110:Colonic Neoplasms / Q000276:immunology* / Q000517:prevention & control; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010957:Plasmids; D014614:Vaccines, Synthetic / Q000276:immunology*
D002272:Carcinoembryonic Antigen; D014614:Vaccines, Synthetic