title: Comparison of the cellular internalization of antibodies used either as immunotoxins or in ADEPT.
abstract: The internalization into tumor cells of two antibodies (C242 and 454A12), which make potent immunotoxins when linked to ricin A-chain, and an antibody (A5B7), which does not make a potent immunotoxin but has proven useful in ADEPT, was evaluated. The 454A12 antibody was rapidly taken into the cells, 50% of the antibody being internalized after 2 h. The C242 antibody was internalized more slowly, approx 50% being taken up by the cells in 24 h. With A5B7, less than 10% of the antibody was internalized after 24 h. Internalization of the C242 antibody was accompanied by the appearance of antibody degradation products in the cell medium after 2 h, and this degradation could be inhibited by addition of a metabolic inhibitor that prevented cell internalization. In contrast, minimal degradation of the A5B7 antibody could be detected up to 24 h after binding to the cells. In conclusion, both 454A12 and C242 antibodies, which make potent immunotoxins, were internalized into tumor cells. The A5B7 antibody, which does not make a potent immunotoxin, was not internalized, and this property may be one reason why A5B7 has proved useful for delivery of enzymes in ADEPT.
authors.affiliation: Cancer Research Department, Zeneca Pharmaceuticals, Macclesfield, Cheshire, UK.
authors.forename: D C
authors.initials: DC
authors.lastname: Blakey
authors.forename: P E
authors.initials: PE
authors.lastname: Pinder
authors.forename: A F
authors.initials: AF
authors.lastname: Wright
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D007111:Immunity, Cellular; D007167:Immunotherapy / Q000379:methods*; D000922:Immunotoxins / Q000627:therapeutic use*; D011355:Prodrugs / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured
chemical_list: D000911:Antibodies, Monoclonal; D000922:Immunotoxins; D011355:Prodrugs