Humanization and characterization of the anti-HLA-DR antibody 1D10.
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.
Kostelny
S A
SA
Protein Design Labs, Inc., Fremont, CA, USA.
Link
B K
BK
Tso
J Y
JY
Vasquez
M
M
Jorgensen
B H
BH
Wang
H
H
Hall
W C
WC
Weiner
G J
GJ
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D000915:Antibody Affinity; D000918:Antibody Specificity; D000920:Antibody-Dependent Cell Cytotoxicity; D017209:Apoptosis / Q000276:immunology; D003001:Cloning, Molecular; D000939:Epitopes / Q000276:immunology; D006684:HLA-DR Antigens / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D015458:Leukemia, T-Cell / Q000276:immunology / Q000473:pathology; D016393:Lymphoma, B-Cell / Q000276:immunology / Q000473:pathology; D051379:Mice; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D000939:Epitopes; D006684:HLA-DR Antigens; D007074:Immunoglobulin G