Phase I study of anticolon cancer humanized antibody XXXX .

@entity1 @entity778 @entity1671 @entity137 @entity1910 @entity13598 @entity694 @entity14 @entity925 @entity5084
PURPOSE: Humanized @entity13598 (huA33; IgG1) monoclonal antibody detects a determinant expressed by 95% of @entity14 and can activate immune cytolytic mechanisms. The present study was designed to (a) define the @entity137 and maximum tolerated dose of huA33 and (b) determine huA33 immunogenicity. EXPERIMENTAL DESIGN: @entity1 (n = 11) with advanced chemotherapy-resistant @entity14 received 4-week cycles of huA33 at 10, 25, or 50 mg/m(2)/week. Serum samples were analyzed using biosensor technology for evidence of @entity778 ( @entity778 ) response. RESULTS: Eight of 11 @entity1 developed a @entity778 response. Significant @entity137 was limited to four @entity1 who developed high @entity778 titers. In two of these cases, infusion-related reactions such as fevers, @entity5084 , facial @entity1671 , and changes in blood pressure were observed, whereas in the other two cases, @entity137 consisted of @entity1910 , fever, or @entity925 . Of three @entity1 who remained @entity778 negative, one achieved a radiographic partial response, with reduction of serum carcinoembryonic antigen from 80 to 3 ng/ml. Four @entity1 had radiographic evidence of stable disease (2, 4, 6, and 12 months), with significant reductions (>25%) in serum carcinoembryonic antigen levels in two cases. CONCLUSIONS: The complementarity-determining region-grafted huA33 antibody is immunogenic in the majority of @entity694 @entity1 (73%). @entity778 activity can be measured reproducibly and quantitatively by BIACORE analysis. Whereas the huA33 construct tested here may be too immunogenic for further clinical development, the antitumor effects observed in the absence of antibody-mediated @entity137 and in this heavily pretreated @entity1 population warrant clinical testing of other IgG1 humanized versions of @entity13598 antibody.
