Immune response to a carcinoembryonic antigen polynucleotide vaccine.
We have constructed a DNA plasmid encoding the full length complementary DNA for human carcinoembryonic antigen (CEA) driven by the cytomegalovirus early promoter/enhancer (plasmid DNA encoding human CEA) and demonstrated that this plasmid can function as a polynucleotide vaccine. This polynucleotide vaccine induced humoral and/or cellular immune responses specific for human CEA in all 5 immunized mice. Lymphoblastic transformation data with the use of enriched T-cell populations detected the presence of CEA-specific memory T-cells in 3 of 5 mice. Lymphocytes from 2 of 5 mice had interleukin 2/interleukin 4 release in response to CEA. CEA specificity was confirmed by the absence of reactivity to a control antigen and lack of CEA reactivity among mice vaccinated with a control plasmid encoding chloramphenicol acetyltransferase. Four of 5 mice vaccinated with plasmid DNA encoding human CEA demonstrated anti-CEA antibody responses. This immune response compared favorably with a positive control group of mice immunized with vaccinia-CEA by a dose and schedule previously shown to induce immunoprotection and therapy against a human CEA expressing syngeneic murine colon carcinoma model. Studies are ongoing to establish the construct, dose, and schedule to elicit optimal CEA-specific immune response as well as immunoprotection and therapy against human CEA expressing syngeneic murine adenocarcinoma models.
Conry
R M
RM
Therapy Program, University of Alabama, Birmingham Comprehensive Cancer Center 35294.
LoBuglio
A F
AF
Kantor
J
J
Schlom
J
J
Loechel
F
F
Moore
S E
SE
Sumerel
L A
LA
Barlow
D L
DL
Abrams
S
S
Curiel
D T
DT
D000818:Animals; D000917:Antibody Formation / Q000187:drug effects / Q000276:immunology; D000918:Antibody Specificity; D002272:Carcinoembryonic Antigen / Q000235:genetics* / Q000276:immunology*; D018076:DNA, Complementary / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007114:Immunization; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism; D008222:Lymphokines / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010957:Plasmids / Q000235:genetics; D011119:Polynucleotides / Q000235:genetics* / Q000276:immunology / Q000494:pharmacology*; D011874:Radiometry; D014614:Vaccines, Synthetic / Q000235:genetics / Q000494:pharmacology*
D002272:Carcinoembryonic Antigen; D018076:DNA, Complementary; D008222:Lymphokines; D011119:Polynucleotides; D014614:Vaccines, Synthetic