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Targeting BCL 1 lymphoma with anti‐idiotype antibodies: Biodistribution kinetics of directly labeled antibodies and bispecific antibody‐targeted bivalent haptens
Author(s) -
Manetti Corine,
Rouvier Eric,
Gautherot Emmanuel,
Loucif Eric,
Barbet Jacques,
Le Doussal Jean Marc
Publication year - 1997
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19970611)71:6<1000::aid-ijc16>3.0.co;2-h
Subject(s) - hapten , bivalent (engine) , radioimmunotherapy , antibody , biodistribution , chemistry , microbiology and biotechnology , immunotherapy , monoclonal antibody , cancer research , immunology , biochemistry , biology , immune system , organic chemistry , metal , in vitro
The mouse BCL 1 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 BCL 1 tumours, using anti‐Id IgG, F(ab') 2 and anti‐Id × anti‐hapten BsF(ab') 2 covalently labelled with 125 iodine, as well as noncovalent complexes of BsF(ab') 2 and 125 I‐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 BCL 1 tumour surface. For radioimmunotherapy, the intracellular targeting of catabolism‐resistant 125 I‐labelled bivalent hapten provides optimal tissue selectivity. Int. J. Cancer 71: 1000‐1009, 1997. © 1997 Wiley‐Liss Inc.