Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET

User menu

  • My alerts
  • Log in
  • My Cart

Search

  • Advanced search
Journal of Pharmacology and Experimental Therapeutics
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET
  • My alerts
  • Log in
  • My Cart
Journal of Pharmacology and Experimental Therapeutics

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Visit jpet on Facebook
  • Follow jpet on Twitter
  • Follow jpet on LinkedIn
Research ArticleINFLAMMATION, IMMUNOPHARMACOLOGY, AND ASTHMA

B-Cell Depletion In Vitro and In Vivo with an Afucosylated Anti-CD19 Antibody

Ronald Herbst, Yue Wang, Sandra Gallagher, Nanette Mittereder, Ellen Kuta, Melissa Damschroder, Rob Woods, Daniel C. Rowe, Li Cheng, Kim Cook, Krista Evans, Gary P. Sims, David S. Pfarr, Michael A. Bowen, William Dall'Acqua, Mark Shlomchik, Thomas F. Tedder, Peter Kiener, Bahija Jallal, Herren Wu and Anthony J. Coyle
Journal of Pharmacology and Experimental Therapeutics October 2010, 335 (1) 213-222; DOI: https://doi.org/10.1124/jpet.110.168062
Ronald Herbst
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yue Wang
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sandra Gallagher
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Nanette Mittereder
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ellen Kuta
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Melissa Damschroder
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Rob Woods
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Daniel C. Rowe
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Li Cheng
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kim Cook
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Krista Evans
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Gary P. Sims
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
David S. Pfarr
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Michael A. Bowen
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
William Dall'Acqua
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Mark Shlomchik
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Thomas F. Tedder
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Peter Kiener
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Bahija Jallal
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Herren Wu
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Anthony J. Coyle
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF
Loading

This article has a correction. Please see:

  • Correction to “B-Cell Depletion In Vitro and In Vivo with an Afucosylated Anti-CD19 Antibody” - January 01, 2011

Abstract

The pan B-cell surface antigen CD19 is an attractive target for therapeutic monoclonal antibody (mAb) approaches. We have generated a new afucosylated anti-human (hu)CD19 mAb, MEDI-551, with increased affinity to human FcγRIIIA and mouse FcγRIV and enhanced antibody-dependent cellular cytotoxicity (ADCC). During in vitro ADCC assays with B-cell lines, MEDI-551 is effective at much lower mAb concentrations than the fucosylated parental mAb anti-CD19-2. Furthermore, the afucosylated CD19 mAb MEDI-551 depleted B cells from normal donor peripheral blood mononuclear cell samples in an autologous ADCC assay, as well as blood and tissue B cells in human CD19/CD20 double transgenic (Tg) mice at lower concentrations than that of the positive control mAb rituximab. In huCD19/CD20 Tg mice, both macrophage-mediated phagocytosis and complement-dependent cytotoxicity contribute to depletion with rituximab; MEDI-551 did not require complement for maximal B-cell depletion. Furthermore, extended B-cell depletion from the blood and spleen was achieved with MEDI-551, which is probably explained by bone marrow B-cell depletion in huCD19/CD20 Tg mice relative to the control mAb rituximab. In summary, MEDI-551 has potent B-cell-depleting activity in vitro and in vivo and may be a promising new approach for the treatment of B-cell malignancies and autoimmune diseases.

Footnotes

  • Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.

    doi:10.1124/jpet.110.168062.

  • ABBREVIATIONS:

    DLBCL
    diffuse large B-cell lymphoma
    mAb
    monoclonal antibody
    ADCC
    antibody-dependent cellular cytotoxicity
    Tg
    transgenic
    CDC
    complement-dependent cytotoxicity
    NK
    natural killer
    PBMC
    peripheral blood mononuclear cell
    PBS
    phosphate-buffered saline
    LDH
    lactate dehydrogenase
    FACS
    fluorescence-activated cell sorting
    CoVF
    cobra venom factor
    BM
    bone marrow.

  • Received March 16, 2010.
  • Accepted July 2, 2010.
  • Copyright © 2010 by The American Society for Pharmacology and Experimental Therapeutics
View Full Text

JPET articles become freely available 12 months after publication, and remain freely available for 5 years. 

Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page. 

 

  • Click here for information on institutional subscriptions.
  • Click here for information on individual ASPET membership.

 

Log in using your username and password

Forgot your user name or password?

Purchase access

You may purchase access to this article. This will require you to create an account if you don't already have one.
Back to top

In this issue

Journal of Pharmacology and Experimental Therapeutics: 381 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 381, Issue 2
1 May 2022
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Index by author
  • Editorial Board (PDF)
  • Front Matter (PDF)
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Journal of Pharmacology and Experimental Therapeutics article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
B-Cell Depletion In Vitro and In Vivo with an Afucosylated Anti-CD19 Antibody
(Your Name) has forwarded a page to you from Journal of Pharmacology and Experimental Therapeutics
(Your Name) thought you would be interested in this article in Journal of Pharmacology and Experimental Therapeutics.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Research ArticleINFLAMMATION, IMMUNOPHARMACOLOGY, AND ASTHMA

B-Cell Depletion In Vitro and In Vivo with an Afucosylated Anti-CD19 Antibody

Ronald Herbst, Yue Wang, Sandra Gallagher, Nanette Mittereder, Ellen Kuta, Melissa Damschroder, Rob Woods, Daniel C. Rowe, Li Cheng, Kim Cook, Krista Evans, Gary P. Sims, David S. Pfarr, Michael A. Bowen, William Dall'Acqua, Mark Shlomchik, Thomas F. Tedder, Peter Kiener, Bahija Jallal, Herren Wu and Anthony J. Coyle
Journal of Pharmacology and Experimental Therapeutics October 1, 2010, 335 (1) 213-222; DOI: https://doi.org/10.1124/jpet.110.168062

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero

Share
Research ArticleINFLAMMATION, IMMUNOPHARMACOLOGY, AND ASTHMA

B-Cell Depletion In Vitro and In Vivo with an Afucosylated Anti-CD19 Antibody

Ronald Herbst, Yue Wang, Sandra Gallagher, Nanette Mittereder, Ellen Kuta, Melissa Damschroder, Rob Woods, Daniel C. Rowe, Li Cheng, Kim Cook, Krista Evans, Gary P. Sims, David S. Pfarr, Michael A. Bowen, William Dall'Acqua, Mark Shlomchik, Thomas F. Tedder, Peter Kiener, Bahija Jallal, Herren Wu and Anthony J. Coyle
Journal of Pharmacology and Experimental Therapeutics October 1, 2010, 335 (1) 213-222; DOI: https://doi.org/10.1124/jpet.110.168062
del.icio.us logo Digg logo Reddit logo Twitter logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Introduction
    • Materials and Methods
    • Results
    • Discussion
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • PK/PD of PDE Inhibitors in Autoimmune Hepatitis
  • Immunopharmacologic Assessment of KPL-404, a CD40 Antagonist
  • RCTR1 Promotes Alveolar Fluid Clearance
Show more Inflammation, Immunopharmacology, and Asthma

Similar Articles

Advertisement
  • Home
  • Alerts
Facebook   Twitter   LinkedIn   RSS

Navigate

  • Current Issue
  • Fast Forward by date
  • Fast Forward by section
  • Latest Articles
  • Archive
  • Search for Articles
  • Feedback
  • ASPET

More Information

  • About JPET
  • Editorial Board
  • Instructions to Authors
  • Submit a Manuscript
  • Customized Alerts
  • RSS Feeds
  • Subscriptions
  • Permissions
  • Terms & Conditions of Use

ASPET's Other Journals

  • Drug Metabolism and Disposition
  • Molecular Pharmacology
  • Pharmacological Reviews
  • Pharmacology Research & Perspectives
ISSN 1521-0103 (Online)

Copyright © 2022 by the American Society for Pharmacology and Experimental Therapeutics