Monoclonal antibody alpha IR-3 inhibits non-small cell lung cancer growth in vitro and in vivo.
The ability of monoclonal antibody (mAb) alpha IR-3 to interact with non-small cell lung cancer (NSCLC) cells was investigated. MAb alpha IR-3 inhibited specific binding of 125I-IGF-I and 125I-alpha IR-3 to a panel of 8 NSCLC cell lines with high affinity (IC50 = 200 and 50 ng/ml, respectively). 125I-alpha IR-3 bound with high affinity (Kd = 40 ng/ml) to a single class of sites (Bmax = 8,000/cell) using NCI-H838 cells. 125I-alpha IR-3 was internalized when exposed to NCI-H838 or H1299 cells at 37 degrees C but not 4 degrees C. alpha IR-3 immunoprecipitated major 90 and 130 kD proteins. IGF-I stimulated and alpha IR-3 inhibited the clonal growth of NCI-H1299 cells. alpha IR-3 slowed the growth of NCI-H157 and H838 xenografts in nude mice. In a biodistribution study 125I-alpha IR-3 was preferentially localized to the tumor as opposed to other organs. These data suggest that IGF-I may be a regulatory agent in NSCLC.
Zia
F
F
Department of Microbiology, George Washington University School of Medicine and Health Sciences, Washington, DC 20037, USA.
Jacobs
S
S
Kull
F
F
Cuttitta
F
F
Mulshine
J L
JL
Moody
T W
TW
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology* / Q000627:therapeutic use; D000918:Antibody Specificity; D002289:Carcinoma, Non-Small-Cell Lung / Q000276:immunology / Q000473:pathology* / Q000517:prevention & control; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008175:Lung Neoplasms / Q000276:immunology / Q000473:pathology* / Q000517:prevention & control; D051379:Mice; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D009368:Neoplasm Transplantation; D011487:Protein Conformation; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured / Q000378:metabolism / Q000637:transplantation; D014410:Tumor Stem Cell Assay
D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D009363:Neoplasm Proteins; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1