Pretargeted radioimmunotherapy of human colorectal xenografts with bispecific antibody and 131I-labeled bivalent hapten.

Unlabelled: We have developed a pretargeting strategy, called the affinity enhancement system (AES), which uses bispecific antibodies to target radiolabeled bivalent haptens to tumor cells. The aim of this study was to evaluate the potential of the AES for the radioimmunotherapy (RIT) of LS174T colorectal xenografts in comparison with RIT with directly labeled F(ab')2 fragment.

Methods: A total of 6 groups of tumor-bearing mice were treated using anticarcinoembryonic antigen (CEA) x anti-diethylenetriamine pentaacetic acid (DTPA)-In bispecific antibody (BsF(ab')2) and 131I-labeled di-DTPA-In bivalent hapten.

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.