Methods of Treating Hematological Malignancies with Notch1 Antibodies

摘要

NOTCH1-binding antibodies and methods of using the antibodies for treating hematologic cancers are disclosed. Methods of using antibodies that bind to a non-ligand binding membrane proximal region of the extracellular domain of human NOTCH1 and methods of treating chronic lymphocytic leukemia (CLL), hairy cell leukemia, chronic myelogenous leukemia (CML), nonHodgkin lymphoma, diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), or cutaneous T-cell lymphoma (CTCL) in a subject, comprising administering a therapeutically effective amount of a NOTCH1-binding antibody to the subject are also disclosed. Methods of identifying subjects suitable for such treatment methods are further disclosed.

主权项

1. A method of treating a hematologic cancer in a human subject comprising administering to the subject a therapeutically effective amount of an antibody that binds human NOTCH1, wherein the antibody comprises:
(a) a heavy chain CDR1 comprising RGYWIE (SEQ ID NO: 15), a heavy chain CDR2 comprising QILPGTGRTNYNEKFKG (SEQ ID NO:16), and a heavy chain CDR3 comprising FDGNYGYYAMDY (SEQ ID NO: 17); and/or (b) a light chain CDR1 comprising RSSTGAVTTSNYAN (SEQ ID NO: 18), a light chain CDR2 comprising GTNNRAP (SEQ ID NO: 19), and a light chain CDR3 comprising ALWYSNHWVFGGGTKL (SEQ ID NO:20), wherein the hematologic cancer is chronic lymphocytic leukemia (CLL), hairy cell leukemia, chronic myelogenous leukemia (CML), non-Hodgkin lymphoma, diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), or cutaneous T-cell lymphoma (CTCL).