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Humanization and characterization of the anti-HLA-DR antibody 1D10

✍ Scribed by Sheri A. Kostelny; Brian K. Link; J. Yun Tso; Max Vasquez; Brett H. Jorgensen; Hong Wang; William C. Hall; George J. Weiner

Publisher
John Wiley and Sons
Year
2001
Tongue
French
Weight
216 KB
Volume
93
Category
Article
ISSN
0020-7136

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✦ Synopsis

1D10 is a previously described antibody that binds to cells from a majority of B-cell malignancies. The current studies were designed to further evaluate the antigen specificity of 1D10 and its potential as an immunotherapeutic agent. Studies with transfectants and immunoprecipitation demonstrated that 1D10 recognizes some, but not all, of the human HLA-DR beta chains. Both normal and malignant B cells can express the 1D10 antigen. A humanized version of 1D10 was produced using CDR grafting. The resulting antibody has an affinity that is similar to that of the parental murine antibody. In addition, the humanized antibody is capable of inducing complement-mediated cytotoxicity, antibody-dependent cell cytotoxicity, and direct apoptosis of 1D10-expressing B cells. Based on these in vitro anti-tumor activities, we conclude humanized 1D10 deserves further evaluation as an immunotherapeutic agent.

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