Frequent anti-V-region immune response to mouse B72.3 monoclonal antibody.
The immune response of 56 colorectal cancer patients to a single infusion of 1 mg of radiolabeled (111In) mouse B72.3-GYK-DTPA immunoconjugate was examined using a double-antigen radiometric assay system. The incidence of antibody response was 48% to polyclonal mouse IgG, 71% to mouse B72.3, and 62% to chimeric B72.3. Twelve patients (23%) had an antibody response to B72.3 V region in the absence of binding to polyclonal mouse IgG. An antiidiotype response was demonstrated in sera from 36% of 25 patients examined and correlated well with chimeric B72.3-GYK-DTPA immunoconjugate binding (r = 0.72, moderately well with mouse B72.3 binding (r = 0.56), and not at all with polyclonal mouse IgG binding (r = 0.28). The peak antibody response occurred most frequently 2 weeks postinfusion, although a "delayed" peak response to chimeric B72.2 occurred in 29% of patients. This study suggests that mouse B72.3 causes an immune response in the majority of patients and that antibody response to the V region is common. Understanding the physiological significance of these antibody responses will require correlation with the kinetics and tumor localization of repeat infusions of such immunoconjugates.
Comprehensive Cancer Center, University of Alabama, Birmingham 35294-3300.
M B
MB
Khazaeli
M N
MN
Saleh
T
T
Liu
P M
PM
Kaladas
S C
SC
Gilman
A F
AF
LoBuglio
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000276:immunology; D002678:Chimera / Q000276:immunology; D015179:Colorectal Neoplasms / Q000276:immunology*; D000939:Epitopes / Q000276:immunology; D006023:Glycoproteins / Q000276:immunology; D006801:Humans; D007127:Immunoglobulin Constant Regions / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D007135:Immunoglobulin Variable Region / Q000276:immunology*; D015592:Immunoradiometric Assay; D007205:Indium Radioisotopes; D051379:Mice; D009842:Oligopeptides / Q000008:administration & dosage; D004369:Pentetic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D000939:Epitopes; D006023:Glycoproteins; D007127:Immunoglobulin Constant Regions; D007074:Immunoglobulin G; D007135:Immunoglobulin Variable Region; D007205:Indium Radioisotopes; D009842:Oligopeptides; C047052:tumor-associated antigen 72; C062250:glycyl-tyrosyl-lysine-DTPA; D004369:Pentetic Acid