Gamma-interferon enhancement of carcinoembryonic antigen expression in human colon carcinoma xenografts.
Athymic nu/nu mice bearing a subcutaneous human colon cancer xenograft (WiDr, low CEA expression) were treated with gamma-interferon (gamma IFN) at varying doses, frequencies, and periods of duration. CEA content (micrograms/g) and uptake of radiolabeled anti-CEA monoclonal antibody (MAB) (percent injected dose per gram, % ID/g) were measured at 48 h following administration of the MAB, The optimal enhancement of tumor CEA content and tumor localization of [111In] anti-CEA monoclonal antibody (MAB) was seen at gamma IFN doses of 100,000 U i.p. every 8 h for 4 days (4.7 micrograms/g; 29% ID/g) compared to control animals (0.9 micrograms/g; 10% ID/g). The effects of gamma IFN on CEA content and MAB localization were less pronounced when administered (a) at lower doses: 5,000 to 50,000 U i.p. every 8 h, (b) at varying frequencies: 300,000 U/day delivered in divided doses every 4 or 24 h, or (c) for varying periods: 2 or 6 days of therapy. In each case, the biologic effects on tumor CEA content and uptake of [111In]MAB correlated closely with the serum gamma IFN level. Therefore, we conclude that enhancement of in vivo CEA expression by gamma IFN may have clinical relevance for tumor imaging and therapy using radiolabeled monoclonal antibodies.
Kuhn
J A
JA
Department of General Oncologic Surgery, City of Hope National Medical Center, Duarte, California 91010.
Wong
J Y
JY
Beatty
B G
BG
Esteban
J M
JM
Williams
L E
LE
Beatty
J D
JD
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D002272:Carcinoembryonic Antigen / Q000378:metabolism*; D003110:Colonic Neoplasms / Q000175:diagnosis / Q000276:immunology* / Q000628:therapy; D005260:Female; D006801:Humans; D007167:Immunotherapy; D007371:Interferon-gamma / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D011994:Recombinant Proteins; D014183:Transplantation, Heterologous
D000911:Antibodies, Monoclonal; D002272:Carcinoembryonic Antigen; D011994:Recombinant Proteins; D007371:Interferon-gamma