title: A nonfucosylated human antibody to CD19 with potent B-cell  depletive activity for therapy of B-cell malignancies.
abstract: A human anti-CD19 antibody was expressed in fucosyltransferase-deficient CHO cells to generate nonfucosylated MDX-1342. Binding of MDX-1342 to human CD19-expressing cells was similar to its fucosylated parental antibody. However, MDX-1342 exhibited increased affinity for FcγRIIIa-Phe158 and FcγRIIIa-Val158 receptors as well as enhanced effector cell function, as demonstrated by increased potency and efficacy in antibody-dependent cellular cytotoxicity (ADCC) and phagocytosis assays. MDX-1342 showed dose-dependent improvement in survival using a murine B-cell lymphoma model in which Ramos cells were administered systemically. In addition, low nanomolar binding to cynomolgus monkey CD19 and increased affinity for cynomolgus monkey FcγRIIIa was observed. In vivo administration of MDX-1342 in cynomolgus monkeys revealed potent B-cell depletion, suggesting its potential utility as a B-lymphocyte depletive therapy for malignancies and autoimmune indications.
authors: Department of Cell Biology and Pharmacology, Medarex, 1324 Chesapeake Terrace, Sunnyvale, CA 94089, USA. pcardarelli@medarex.com
authors: Pina M
authors: PM
authors: Cardarelli
authors: Chetana
authors: C
authors: Rao-Naik
authors: Sharline
authors: S
authors: Chen
authors: Haichun
authors: H
authors: Huang
authors: Amie
authors: A
authors: Pham
authors: Maria-Cristina
authors: MC
authors: Moldovan-Loomis
authors: Chin
authors: C
authors: Pan
authors: Ben
authors: B
authors: Preston
authors: David
authors: D
authors: Passmore
authors: Jie
authors: J
authors: Liu
authors: Michelle R
authors: MR
authors: Kuhne
authors: Alison
authors: A
authors: Witte
authors: Diann
authors: D
authors: Blanset
authors: David J
authors: DJ
authors: King
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000276:immunology / Q000627:therapeutic use*; D000915:Antibody Affinity; D018941:Antigens, CD19 / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D006801:Humans; D008212:Lymphocyte Depletion; D016393:Lymphoma, B-Cell / Q000628:therapy*; D008252:Macaca fascicularis; D051379:Mice; D016513:Mice, SCID; D008822:Mice, Transgenic; D010587:Phagocytosis; D017452:Receptors, IgG / Q000276:immunology; D023041:Xenograft Model Antitumor Assays
chemical_list: D000911:Antibodies, Monoclonal; D018941:Antigens, CD19; C557496:MDX-1342 antibody; D017452:Receptors, IgG