Epidermal growth factor receptor monoclonal antibodies inhibit the growth of lung cancer cell lines.
The ability of monoclonal antibody (MAb 108), an immunoglobulin G (IgG)2a against the epidermal growth factor receptor (EGF-R), to interact with lung cancer cell lines was investigated. 125I-EGF bound with high affinity to non-small-cell lung cancer (NSCLC) cells, and MAb 108 inhibited specific binding of nine NSCLC cell lines in a dose-dependent manner (IC50 = 0.3-3 micrograms per ml). 125I-MAb 108 bound with high affinity (kd = 2 nM) to a single class of sites (Bmax = 70,000 per cell) using NSCLC neuroendocrine cell line NCI-H460. Specific 125I-MAb 108 binding was inhibited with high affinity by MAb 108 but not by a control antibody IgG using large-cell carcinoma cell line NCI-H1299. 125I-MAb 108 binding was not internalized at 37 degrees C using NSCLC neuroendocrine cell line NCI-H460 and adenocarcinoma cell line NCI-H23. Also, 1 microgram per ml of MAb 108 but not of a control IgG inhibited the clonal growth of NCI-H23 and squamous cell carcinoma cell line NCI-H157 in vitro. Also, MAb 108 inhibited xenograft formation of cell lines NCI-H460, NCI-H157, and NCI-H727 in nude mice in vivo. After a palpable tumor had formed using NCI-H460 cells, injection of 100 micrograms of MAb 108 (intraperitoneally three times weekly) inhibited xenograft volume in nude mice by approximately 50%. These data suggest that MAb 108 may interact with EGF receptors on lung cancer cell lines and inhibit NSCLC proliferation.
Lee
M
M
Department of Biochemistry and Molecular Biology, George Washington University Medical Center, Washington, D.C.
Draoui
M
M
Zia
F
F
Gazdar
A
A
Oie
H
H
Bepler
G
G
Bellot
F
F
Tarr
C
C
Kris
R
R
Moody
T W
TW
D000818:Animals; D000911:Antibodies, Monoclonal; D002289:Carcinoma, Non-Small-Cell Lung / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D066246:ErbB Receptors / Q000276:immunology / Q000502:physiology*; D005260:Female; D008175:Lung Neoplasms / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D066246:ErbB Receptors