Induction of anti-tumor immunity by intrasplenic administration of a carcinoembryonic antigen DNA vaccine.
BACKGROUND
We have previously reported that intramuscular, intradermal or epidermal gene gun administration of a plasmid encoding carcinoembryonic antigen (CEA) under transcriptional regulatory control of the cytomegalovirus (CMV) early promoter/enhancer elicits CEA-specific humoral and cellular immune responses in mice with resultant immunoprotection against challenge with syngeneic, CEA-expressing colon adenocarcinoma cells.


METHODS
In the present work, we examine the ability of this DNA vaccine construct (pCEA) to elicit CEA-specific immunity following intrasplenic administration. Groups of mice were immunized with pCEA by intrasplenic or intramuscular injection. Six weeks later, mice were evaluated for the presence of anti-CEA humoral responses and were challenged with syngeneic, CEA-expressing colon carcinoma cells.


RESULTS
Intrasplenic administration of pCEA produced a frequency of CEA-specific antibody responses comparable to that elicited by intramuscular pCEA inoculation. Both intrasplenic and intramuscular administration of pCEA generated IgG2a antibody responses to CEA, consistent with the induction of T helper-1-biased immune responses. In addition, partial immunoprotection against tumor challenge was observed after a single plasmid DNA dose by either route of administration. Subsequent studies revealed that antibody responses to intrasplenic DNA vaccination are dose and schedule dependent.


CONCLUSIONS
These findings support future investigations of DNA vaccination strategies that specifically promote the uptake of plasmid by splenocytes.
White
S A
SA
Department of Medicine, Comprehensive Cancer Center, University of Alabama at Birmingham, USA.
LoBuglio
A F
AF
Arani
R B
RB
Pike
M J
MJ
Moore
S E
SE
Barlow
D L
DL
Conry
R M
RM
D000818:Animals; D000917:Antibody Formation; D002272:Carcinoembryonic Antigen / Q000235:genetics / Q000276:immunology*; D003110:Colonic Neoplasms / Q000276:immunology / Q000517:prevention & control*; D003587:Cytomegalovirus / Q000235:genetics; D005260:Female; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D007267:Injections; D051379:Mice; D008810:Mice, Inbred C57BL; D011401:Promoter Regions, Genetic; D013154:Spleen; D014407:Tumor Cells, Cultured; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000494:pharmacology*
D002272:Carcinoembryonic Antigen; D019444:Vaccines, DNA