Carcinoembryonic antigen and alpha-fetoprotein expression and monoclonal antibody targeting in a human hepatoma/nude mouse model.
Hep G2, a human hepatocellular carcinoma, was grown s.c. in nude mice, as well as in tissue culture. This line retains the normal liver parenchymal cell capacity to synthesize human plasma proteins such as albumin, but there is no indication that it harbors the hepatitis B virus. We have detected the oncofetal antigens alpha-fetoprotein (AFP) and carcinoembryonic antigen (CEA) in both Hep G2 xenografts and spent tissue culture media by Ouchterlony double diffusion assays, enzyme-linked immunosorbent assay, and immunohistology. By enzyme-linked immunosorbent assay, the AFP levels were 544.9 ng/ml in the cell culture and 1.6 microgram/g in saline extracts of the xenograft. The CEA levels were 35.2 ng/ml in the cell culture and 5.4 micrograms/g in the xenograft. The biodistribution of a radioiodinated anti-AFP murine monoclonal antibody and an anti-CEA monoclonal antibody were studied separately in nude mice bearing s.c. Hep G2 xenografts in comparison to an isotype-matched irrelevant IgG (Ag8). Anti-CEA antibody showed a preferential localization for Hep G2, but anti-AFP antibody did not. Immunohistochemical studies of the Hep G2 tumor, using biotinylated anti-AFP and anti-CEA, indicate both cytoplasmic and luminal staining of CEA and AFP in the tumor. These results suggest that Hep G2 may be a useful cell line for radioimmunodetection and radioimmunotherapy studies using anti-CEA and possibly anti-AFP monoclonal antibodies.
Center for Molecular Medicine and Immunology, University of Medicine and Dentistry of New Jersey, Newark 07103.
Z F
ZF
Wang
R
R
Stein
R M
RM
Sharkey
D M
DM
Goldenberg
D000818:Animals; D000911:Antibodies, Monoclonal; D002272:Carcinoembryonic Antigen / Q000032:analysis* / Q000276:immunology; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes / Q000378:metabolism; D008114:Liver Neoplasms, Experimental / Q000276:immunology*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D014018:Tissue Distribution; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D000509:alpha-Fetoproteins / Q000032:analysis* / Q000276:immunology
D000911:Antibodies, Monoclonal; D002272:Carcinoembryonic Antigen; D007457:Iodine Radioisotopes; D000509:alpha-Fetoproteins