title: A glycoengineered anti-CD19 antibody with potent antibody-dependent cellular cytotoxicity activity in vitro and lymphoma growth inhibition in vivo.
abstract: Human cluster of differentiation (CD) antigen 19 is a B cell-specific surface antigen and an attractive target for therapeutic monoclonal antibody (mAb) approaches to treat malignancies of B cell origin. MEDI-551 is an affinity-optimized and afucosylated CD19 mAb with enhanced antibody-dependent cellular cytotoxicity (ADCC). The results from in vitro ADCC assays with Natural Killer cells as effector cells, demonstrate that MEDI-551 is effective at lower mAb doses than rituximab with multiple cell lines as well as primary chronic lymphocytic leukaemia and acute lymphoblastic leukaemia samples. Targeting CD19 with MEDI-551 was also effective in several severe combined immunodeficiency lymphoma models. Furthermore, the combination of MEDI-551 with rituximab resulted in prolonged suppression of tumour growth, demonstrating that therapeutic mAbs with overlapping effector function can be combined for greater tumour growth inhibition. Together, the data demonstrate that MEDI-551 has potent antitumour activity in preclinical models of B cell malignancies. The results also suggest that the combination of the ADCC-enhanced CD19 mAb with an anti-CD20 mAb could be a novel approach for the treatment of B cell lymphomas.
authors: Department of Research, MedImmune, LLC, Gaithersburg, MD 20787, USA.
authors: Elizabeth
authors: E
authors: Ward
authors: Nanette
authors: N
authors: Mittereder
authors: Ellen
authors: E
authors: Kuta
authors: Gary P
authors: GP
authors: Sims
authors: Michael A
authors: MA
authors: Bowen
authors: William
authors: W
authors: Dall'Acqua
authors: Thomas
authors: T
authors: Tedder
authors: Peter
authors: P
authors: Kiener
authors: Anthony J
authors: AJ
authors: Coyle
authors: Herren
authors: H
authors: Wu
authors: Bahija
authors: B
authors: Jallal
authors: Ronald
authors: R
authors: Herbst
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology*; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage; D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects; D018941:Antigens, CD19 / Q000276:immunology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D015448:Leukemia, B-Cell / Q000276:immunology* / Q000628:therapy*; D016393:Lymphoma, B-Cell / Q000276:immunology* / Q000628:therapy*; D051379:Mice; D016513:Mice, SCID; D015202:Protein Engineering / Q000379:methods; D011961:Receptors, Fc / Q000276:immunology; D000069283:Rituximab; D023041:Xenograft Model Antitumor Assays
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018941:Antigens, CD19; D011961:Receptors, Fc; D000069283:Rituximab