Apr 30, 2009

In vitro and in vivo characterization of MDX-1401 for therapy of malignant lymphoma

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Pina M CardarelliDavid J King

Abstract

This study was undertaken to evaluate the effects of MDX-1401, a nonfucosylated fully human monoclonal antibody that binds to human CD30, and to determine whether it exhibits greater in vitro and in vivo activity than its parental antibody. Assays measuring antibody binding to CD30-expressing cells and FcgammaRIIIa (CD16) transfectants as well as antibody-dependent cellular cytotoxicity (ADCC) were conducted. Antitumor activity was determined using a Karpas-299 systemic model. The binding of MDX-1401 to CD30 antigen was identical to fucose-containing parental anti-CD30 antibody (MDX-060). In contrast, MDX-1401 showed increased binding affinity to FcgammaRIIIa-transfected cells resulting in increased effector function. MDX-1401 greatly improved ADCC activity as evidenced by a decrease in half-maximal effective concentration (EC(50)) and an increase in maximum cell lysis when compared with MDX-060. Increased ADCC activity was observed among a panel of cell lines, including one with very low CD30 antigen expression in which parental antibody failed to induce any detectable ADCC. MDX-1401 activity with all FcgammaRIIIa polymorphic variants, including less active Phe/Phe158 and Phe/Val158 effector cells, was shown. Furthermore, MDX-...Continue Reading

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Mentioned in this Paper

Pathologic Cytolysis
Cricetulus
Monoclonal Antibodies
FCGR3B protein, human
Xenograft Model Antitumor Assays
Antigens, CD16
Binding Sites, Antibody
Chinese Hamster Ovary Cell
Antibody Avidity
Leu-11 Antigens

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