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Humanization and characterization of the anti‐HLA‐DR antibody 1D10
Author(s) -
Kostelny Sheri A.,
Link Brian K.,
Tso J. Yun,
Vasquez Max,
Jorgensen Brett H.,
Wang Hong,
Hall William C.,
Weiner George J.
Publication year - 2001
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/ijc.1366
Subject(s) - antibody , cytotoxicity , humanized antibody , antigen , human leukocyte antigen , immunoprecipitation , complement dependent cytotoxicity , immunology , in vitro , biology , microbiology and biotechnology , humanized mouse , cancer research , chemistry , antibody dependent cell mediated cytotoxicity , immune system , monoclonal antibody , biochemistry
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 β 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. © 2001 Wiley‐Liss, Inc.