Comparison of in vitro cell binding characteristics of four monoclonal antibodies and their individual tumor localization properties in mice.
Although many antibodies are being used for imaging studies, it is not clear which in vitro properties of antibodies will best reflect their in vivo characteristics. The ability to correlate in vitro binding characteristics of monoclonal antibodies to tumor antigens with their in vivo localization characteristics, particularly with respect to tumor localization properties, is desirable for rapid selection of monoclonal antibodies with potential for clinical use. The in vitro binding characteristics of three monoclonal antibodies to the murine Ly-2.1 antigen and one to the Ly-3.1 antigen have been studied on cultured tumor cells bearing these antigens. The association and dissociation rate constants, apparent affinity, and immunoreactivity of each antibody in vitro were compared with their ability to localize the s.c. tumors from the same cell line growing in Ly-2.1-/Ly-3.1-mice. The antibody with the highest affinity and fastest association rate localized to tumor at the earliest time (16-20 h after injection) and had the highest percentage of the injected dose/g in the tumor (greater than 25%). The antibody with the lowest affinity showed significantly less localization to tumor cells, compared with the other three antibodies. The ranking of the antibodies by affinity agreed with the ranking in terms of their ability to localize to tumors, but the in vitro immunoreactivity of the antibodies, as measured by a cell binding assay, did not correlate with their tumor localization properties. Immunoscintigraphic studies did not precisely correlate with biodistribution data or in vitro binding characteristics, because tumors could be satisfactorily imaged with each antibody, although it was noted that the antibody with the highest affinity gave the best image. The results indicate that kinetic binding parameters and affinity of monoclonal antibodies may be useful in predicting their potential for tumor localization and that kinetics of association of antibodies in vitro may predict localization kinetics in vivo.
Andrew
S M
SM
Department of Pathology, University of Melbourne, Parkville, Victoria, Australia.
Johnstone
R W
RW
Russell
S M
SM
McKenzie
I F
IF
Pietersz
G A
GA
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000915:Antibody Affinity; D000936:Antigen-Antibody Complex / Q000032:analysis; D000950:Antigens, Ly / Q000276:immunology*; D006207:Half-Life; D007457:Iodine Radioisotopes; D051379:Mice; D008815:Mice, Inbred Strains; D011877:Radionuclide Imaging; D013945:Thymoma / Q000000981:diagnostic imaging* / Q000276:immunology; D013953:Thymus Neoplasms / Q000000981:diagnostic imaging* / Q000276:immunology; D014018:Tissue Distribution
D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D000950:Antigens, Ly; D007457:Iodine Radioisotopes