Rapid and specific targeting of monoclonal antibody A33 to a @entity694 xenograft in XXXX .

@entity1 @entity5 @entity19 @entity2866 @entity13599 @entity694 @entity70674
Monoclonal antibody (mAb) A33 detects a glycoprotein homogeneously expressed by > 95% of @entity1 @entity694 and by normal colon cells. The @entity13599 is not secreted or shed and after mAb A33 binds to antigen on the cell membrane, a fraction of membrane-bound mAb A33 is internalized into endosomes. Phase @entity70674 -mAb A33 biodistribution studies have shown consistent, specific @entity5 -targeting, and phase I radioimmunotherapy trials with 131I- or 125I-mAb A33 have demonstrated antitumor effects. Here we describe a nude @entity19 model that was established using a @entity1 @entity694 cell line, SW1222, which grows as a relatively hypovascular, invasive heterotransplant when injected i.m. Peak uptake of 131I-labeled or 111In-chelated mAb A33 was observed at 48-96 h, with a mean of 34% (SE +/- 5.0) and 46.7% (SE +/- 1.7) injected dose per gram of @entity5 tissue, respectively. 111In-mAb A33 was retained in @entity5 tissue longer than @entity2866 radioimmunoconjugates. The specificity of antibody localization was assessed using a control antibody ( @entity5 uptake and pharmacokinetics), a control @entity5 , corrections for vascular antibody blood-pooling in @entity5 tissue, and blocking of radiolabeled mAb A33 localization by pretreating @entity19 with excess unlabeled mAb A33. These experiments demonstrate that mAb A33 localization in @entity5 was specific, and they emphasize the unexpected rapidity with which the antibody localizes. Our conclusions were confirmed by immunohistochemical techniques which allowed direct visualization of localization and distribution of the humanized version of mAb A33 in @entity5 tissue. Furthermore, antibody doses approximating @entity5 -saturating doses demonstrated that a homogeneous distribution of antibody in @entity5 is possible. This model will be valuable for studies focusing on general physiologic aspects of antibody-to- @entity5 cell localization and critical as a guide to the evaluation of various A33 antibody constructs and combinations with other therapies for the treatment of @entity694 .
