Establishment of a rat colonic carcinoma model for study of immunoreagents against the human tumor-associated TAG72 antigen.
TAG72 originally defined by the mouse B72.3 antibody is a mucin-like, human tumor-associated antigen present in more than 85% of human colonic adenocarcinomas. Establishment of a tumor model expressing the TAG72 antigen in immunocompetent animals would be of great benefit in evaluating the therapeutic efficacy and studying anti-tumor immune mechanisms of anti-TAG72 immunoreagents. In this study, we screened 6 animal tumor cell lines including 3 derived from mouse colonic adenocarcinomas (MCR-26, MCR-38-LD and CA-51), 1 from mouse ovarian adenocarcinoma (MOT), 1 from rat colonic adenocarcinoma LMCR, and 1 from rat mammalial adenocarcinoma (R3230AB) for TAG72 expression by using the B72.3 antibody. Immunohistochemistry disclosed significant amounts of TAG72-expression in the dimethylhydrazine-induced BDIX rat colonic adenocarcinoma LMCR. The rat TAG72 antigen purified from rat LMCR tumors showed strong immunoreactivity for the B72.3 antibody in ELISA analysis and displayed a smear band of high molecular weight in Western blotting, which is similar to the human TAG72 antigen purified from human LS174T colonic adenocarcinoma. In addition, the iodinated B72.3 antibody was able to localize LMCR tumor in BDIX rats. Therefore, this rat LMCR model should be useful in studying human colonic cancer, especially in evaluating the therapeutic efficacy of anti-TAG72 immunoreagents such as the recombinant fusion proteins possessing the anti-TAG72 antibody fragment and the cytokine moiety.
Xiang
J
J
Saskatoon Cancer Center, University of Saskatchewan, Canada.
Moyana
T
T
Matte
G
G
Wilkinson
A
A
Itzkowitz
S
S
Qi
Y
Y
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000951:Antigens, Neoplasm / Q000032:analysis / Q000276:immunology*; D002455:Cell Division; D003110:Colonic Neoplasms / Q000628:therapy*; D004195:Disease Models, Animal; D005434:Flow Cytometry; D006023:Glycoproteins / Q000032:analysis / Q000276:immunology*; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D051381:Rats
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D006023:Glycoproteins; C047052:tumor-associated antigen 72