The advantage of residualizing radiolabels for targeting B-cell lymphomas with a radiolabeled anti-CD22 monoclonal antibody.
CD22 antibodies (Abs) bound to B-cell lymphomas are known to be internalized and catabolized rapidly. Therefore, it would be expected that use of CD22 as a target for radioimmunotherapy should be enhanced by the use of "residualizing" radiolabels, which are trapped within the cell after catabolism of the Ab to which they had been conjugated. Our study was intended to evaluate this hypothesis using Ab LL2. In initial experiments, we found that LL2 binding was strongly temperature dependent, with approximately 15-fold greater binding at 37 degrees C than at 0 degrees C. A series of experiments suggested that this difference is due to a conformational change in the antigen at low temperature, so that the LL2 epitope is partially blocked. In vitro, residualizing labels-including 125I-dilactitol tyramine and 111In-DTPA-were retained by cells much longer than a conventional iodine label. In vivo, residualizing labels also showed a marked advantage in terms of uptake by Ramos B-cell lymphoma xenografts in nude mice. However, the absolute Ab uptake by xenografts was quite low, in comparison with results obtained with many carcinoma xenografts, which appears to be due in part to vascular properties of the B-cell lymphoma xenografts.
Mattes
M J
MJ
Garden State Cancer Center at the Center for Molecular Medicine and Immunology, Belleville, NJ 07109, USA.
Shih
L B
LB
Govindan
S V
SV
Sharkey
R M
RM
Ong
G L
GL
Xuan
H
H
Goldenberg
D M
DM
D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics; D015703:Antigens, CD / Q000276:immunology*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000276:immunology*; D015815:Cell Adhesion Molecules / Q000276:immunology; D006801:Humans; D007205:Indium Radioisotopes / Q000493:pharmacokinetics; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics; D037102:Lectins; D008657:Metabolic Clearance Rate; D051379:Mice; D008819:Mice, Nude; D004369:Pentetic Acid / Q000493:pharmacokinetics; D016719:Radioimmunodetection / Q000379:methods*; D051918:Sialic Acid Binding Ig-like Lectin 2; D013997:Time Factors; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; C497867:CD22 protein, human; C497868:Cd22 protein, mouse; D015815:Cell Adhesion Molecules; D007205:Indium Radioisotopes; D007457:Iodine Radioisotopes; D037102:Lectins; D051918:Sialic Acid Binding Ig-like Lectin 2; D004369:Pentetic Acid