Humanized Anti-HLA-DR Antibodies

摘要

The present invention concerns compositions and methods of use of humanized anti-HLA-DR antibodies. In preferred embodiments, the antibodies induce apoptosis and inhibit proliferation of lymphoma cells without inducing CDC or ADCC. In more preferred embodiments, the humanized anti-HLA-DR antibodies bind to the same epitope of HLA-DR as, or compete for binding to HLA-DR with, a murine L243 antibody. Most preferably, the humanized anti-HLA-DR antibody exhibits a higher affinity for HLA-DR than the parental murine antibody. The humanized HLA-DR antibody is of use for therapy of various diseases such as cancer, autoimmune disease or immune dysregulatory function, and is of particular use for therapy of B cell lymphomas and leukemias. In most preferred embodiments, the humanized anti-HLA-DR antibody is capable of inducing at least partial remission of lymphomas that are resistant to other B cell antibodies, such as rituximab.

主权项

1. A method of delivering a therapeutic or diagnostic agent to an HLA-DR positive cell comprising:
a) obtaining an immunoconjugate comprising (i) a humanized anti-HLA-DR antibody or antigen-binding fragment thereof that competes for binding to HLA-DR with a murine L243 antibody comprising the heavy chain complementarity determining region (CDR) sequences CDR1 (NYGMN, SEQ ID NO: 39), CDR2 (WINTYTREPTYADDFKG, SEQ ID NO: 40), and CDR3 (DITAVVPTGFDY, SEQ ID NO: 41) and the light chain CDR sequences CDR1 (RASENIYSNLA, SEQ ID NO: 42), CDR2 (AASNLAD, SEQ ID NO: 43), and CDR3 (QHFWTTPWA, SEQ ID NO: 44), conjugated to (ii) a therapeutic or diagnostic agent; and b) exposing an HLA-DR positive cell to the immunoconjugate.