Inhibition of hepatic metastases of human colon cancer in nude mice by a chimeric SF-25 monoclonal antibody.
OBJECTIVE
Hepatic metastasis is one of the most serious complications of human colon cancer. A murine-human chimeric SF-25 monoclonal antibody was prepared, and this construct recognizes a cell surface antigen highly present in human colon adenocarcinoma.


METHODS
This study determined if the chimeric SF-25 monoclonal antibody inhibits the outgrowth of hepatic metastases of human colon adenocarcinoma using an athymic nude mouse model.


RESULTS
A single intravenous injection of chimeric SF-25 monoclonal antibody significantly inhibited the outgrowth of 5- and 7-day hepatic micrometastases (P = 0.0001 and 0.004, respectively, vs. untreated) and improved the survival of the animals. No detectable tumor was found in the liver when mice were treated by multiple injections of the antibody immediately after tumor cell grafting into the portal vein. In contrast, F(ab')2 fragments did not show antitumor effects, and the administration of natural killer cell or macrophage depleting agents (anti-asialo GM1 antibody and carrageenan, respectively) substantially inhibited the antitumor effects of chimeric SF-25 monoclonal antibody in vivo.


CONCLUSIONS
Chimeric SF-25 monoclonal antibody inhibits growth of hepatic metastasis of human colon cancer, and cell-mediated host immune mechanisms seem to be important for its in vivo antitumor activity.
Takahashi
H
H
Gastrointestinal Unit, Massachusetts General Hospital, Boston.
Nakada
T
T
Nakaki
M
M
Wands
J R
JR
D000230:Adenocarcinoma / Q000401:mortality / Q000517:prevention & control* / Q000556:secondary*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000235:genetics / Q000494:pharmacology*; D000920:Antibody-Dependent Cell Cytotoxicity; D002678:Chimera; D003110:Colonic Neoplasms / Q000473:pathology*; D003165:Complement System Proteins / Q000502:physiology; D003602:Cytotoxicity, Immunologic; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology / Q000473:pathology; D008113:Liver Neoplasms / Q000401:mortality / Q000517:prevention & control* / Q000556:secondary*; D008264:Macrophages / Q000276:immunology / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D016019:Survival Analysis; D014183:Transplantation, Heterologous
D000911:Antibodies, Monoclonal; D003165:Complement System Proteins