A carcinoembryonic antigen polynucleotide vaccine has in vivo antitumor activity.
We have constructed a plasmid DNA encoding the full-length cDNA for human carcinoembryonic antigen (CEA) driven by the cytomegalovirus early promoter/enhancer and demonstrated that this plasmid can function as a polynucleotide vaccine. The immune response elicited by the CEA polynucleotide vaccine is dose and schedule dependent. There appears to be a threshold dose of 50 micrograms capable of inducing CEA-specific lymphoblastic transformation, lymphokine release, and antibody response. Doses of 10 micrograms were significantly less effective. When 50-micrograms doses are employed, thrice weekly or weekly vaccination schedules more reliably elicit CEA-specific immune responses by day 43 than does an every-3-weeks schedule. Furthermore the CEA polynucleotide vaccine can immunoprotect against challenge with syngeneic CEA-transduced colon carcinoma cells as early as 3 weeks after the first vaccination. Studies are ongoing to demonstrate the ability of CEA polynucleotide vaccination to treat pre-existing syngeneic mouse colon and breast carcinomas expressing human CEA.
Conry
R M
RM
Department of Medicine, University of Alabama at Birmingham 35294.
LoBuglio
A F
AF
Loechel
F
F
Moore
S E
SE
Sumerel
L A
LA
Barlow
D L
DL
Curiel
D T
DT
D000818:Animals; D000912:Antibodies, Neoplasm / Q000096:biosynthesis; D002272:Carcinoembryonic Antigen / Q000235:genetics* / Q000276:immunology*; D003110:Colonic Neoplasms / Q000276:immunology / Q000628:therapy*; D015870:Gene Expression; D015316:Genetic Therapy / Q000379:methods*; D007378:Interleukins / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D010957:Plasmids; D014407:Tumor Cells, Cultured; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*
D000912:Antibodies, Neoplasm; D002272:Carcinoembryonic Antigen; D007378:Interleukins; D014614:Vaccines, Synthetic