[PROC. AMER. ASSOC. CANCER RES. 40, March 1999]
Copyright © 1999 by the American Association for Cancer Research
#2794 DNA vaccines based on the structure of an anti-idiotype antibody (3H1) mimicking
carcinoembryonic antigen (CEA). Manna, S., Tripathi, P.K., Qin, H-X., Bhattacharya-Chatterjee, M., Foon, K.A.
and Chatterjee, S.K. The Lucille Parker Markey Cancer Center, University of Kentucky Medical Center,
Lexington, KY 40536.
Anti-idiotype antibody 3H1 was produced by immunization of mice with the anti-CEA monoclonal antibody, 8019.
3H1 mimics CEA and acts as a surrogate for CEA. The goal of this work was to determine the efficacy of plasmids
expressing single chain variable fragments (scFv) of 3H1 (p3H1) as tumor vaccines. Female C57BL/6 mice were
vaccinated intramuscularly with 100 µg of p3H1. Sera were drawn from the tail vein before every biweekly
vaccination. Induction of anti-CEA antibodies in the sera was determined by ELISA. Anti-CEA antibody was induced
in 5 out of 11 mice after the first vaccination and the titer increased with every vaccination up to 6 vaccinations.
Cytokines, such as GM-CSF and IL-2 have been reported to augment the immune response of DNA vaccines.
However, inclusion of 200 ng of murine GM-CSF in the p3H1 vaccine had no effect on the anti-CEA antibody
response. Two more plasmids were constructed by incorporation of GM-CSF cDNA in the p3H1. One plasmid,
ps-GM was designed to secrete GM-CSF and 3H1 scFv in the transfected cells, while pf-GM was designed to
express a fusion protein of 3H1 scFv and GM-CSF. While vaccination with ps-GM had no effect on immune
response, pf-GM induced anti-CEA antibody in a greater proportion of mice (6 out of 9) and the mean antibody titer
was significantly higher than that induced by p3H1. Plasmid pf-GM appears to be a better DNA vaccine than p3H1
for induction of anti-CEA immune responses. Supported in part by NIH grants RO1 CA72773 and RO1 CA72018. |
