Targeting BCL1 lymphoma with anti-idiotype antibodies: biodistribution kinetics of directly labeled antibodies and bispecific antibody-targeted bivalent haptens.
The mouse BCL1 lymphoma model has been used for evaluating immunotherapy with anti-idiotype (anti-Id) antibodies, including Id immunisation, IgG therapy and bispecific (Bs) antibody-targeted cytotoxicity. Here, we provide quantitative data on the targeting of small (25 +/- 12 mg) intrasplenic BCL1 tumours, using anti-Id IgG, F(ab')2 and anti-Id x anti-hapten BsF(ab')2 covalently labelled with 125iodine, as well as noncovalent complexes of BsF(ab')2 and 125I-labelled bivalent hapten. The results are the following: 1) up to 115% of the injected dose per gram (% ID/g) of spleen can be localised in the first hour, corresponding to approximately 600% ID/g of tumour; 2) localisation is specific for cell-surface Id; 3) optimal doses can overcome circulating Id; 4) circulating Id markedly increases the catabolism of IgG, thus impairing tumour localisation; 5) bivalent reagents are internalised by the target cells; 6) iodine covalently bound to bivalent antibodies [IgG, F(ab')2] is rapidly (T(1/2): 6-9 hr) released from the tumour; in contrast, the bivalent hapten is retained for a longer time (T(1/2): 25 hr); and 7) in the absence of bivalent hapten, the monovalent BsF(ab')2 is not rapidly internalised and dissociates from tumour cell-surface Id. Our results suggest that monovalent anti-Id, lacking Fc, can efficiently be targeted to the BCL1 tumour surface. For radioimmunotherapy, the intracellular targeting of catabolism-resistant 125I-labelled bivalent hapten provides optimal tissue selectivity.
Manetti
C
C
Imaging and Therapeutics Department, Immunotech SA, Marseille, France.
Rouvier
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E
Gautherot
E
E
Loucif
E
E
Barbet
J
J
Le Doussal
J M
JM
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology*; D018033:Antibodies, Bispecific / Q000276:immunology*; D002455:Cell Division / Q000276:immunology; D006241:Haptens / Q000276:immunology*; D007457:Iodine Radioisotopes; D016393:Lymphoma, B-Cell / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D013154:Spleen / Q000276:immunology
D000888:Antibodies, Anti-Idiotypic; D018033:Antibodies, Bispecific; D006241:Haptens; D007457:Iodine Radioisotopes