A nonfucosylated human antibody to CD19 with potent B-cell  depletive activity for therapy of B-cell malignancies.
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.
Cardarelli
Pina M
PM
Department of Cell Biology and Pharmacology, Medarex, 1324 Chesapeake Terrace, Sunnyvale, CA 94089, USA. pcardarelli@medarex.com
Rao-Naik
Chetana
C
Chen
Sharline
S
Huang
Haichun
H
Pham
Amie
A
Moldovan-Loomis
Maria-Cristina
MC
Pan
Chin
C
Preston
Ben
B
Passmore
David
D
Liu
Jie
J
Kuhne
Michelle R
MR
Witte
Alison
A
Blanset
Diann
D
King
David J
DJ
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
D000911:Antibodies, Monoclonal; D018941:Antigens, CD19; C557496:MDX-1342 antibody; D017452:Receptors, IgG