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01.02.2010 | Original Article

A nonfucosylated human antibody to CD19 with potent B-cell depletive activity for therapy of B-cell malignancies

verfasst von: Pina M. Cardarelli, Chetana Rao-Naik, Sharline Chen, Haichun Huang, Amie Pham, Maria-Cristina Moldovan-Loomis, Chin Pan, Ben Preston, David Passmore, Jie Liu, Michelle R. Kuhne, Alison Witte, Diann Blanset, David J. King

Erschienen in: Cancer Immunology, Immunotherapy | Ausgabe 2/2010

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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.

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Titel: A nonfucosylated human antibody to CD19 with potent B-cell depletive activity for therapy of B-cell malignancies
verfasst von: Pina M. Cardarelli
Chetana Rao-Naik
Sharline Chen
Haichun Huang
Amie Pham
Maria-Cristina Moldovan-Loomis
Chin Pan
Ben Preston
David Passmore
Jie Liu
Michelle R. Kuhne
Alison Witte
Diann Blanset
David J. King
Publikationsdatum: 01.02.2010
Verlag: Springer-Verlag
Erschienen in: Cancer Immunology, Immunotherapy / Ausgabe 2/2010
Print ISSN: 0340-7004
Elektronische ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-009-0746-z

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24.04.2024 | DGIM 2024 | Nachrichten

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A nonfucosylated human antibody to CD19 with potent B-cell depletive activity for therapy of B-cell malignancies

Abstract

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