Design, construction, and in vitro analyses of multivalent antibodies

Kathy Miller, Gloria Meng, Jun Liu, Amy Hurst, Vanessa Hsei, Wai Lee Wong, Rene Ekert, David Lawrence, Steven Sherwood, Laura DeForge, Jacques Gaudreault, Gilbert Keller, Mark Sliwkowski, Avi Ashkenazi, Leonard Presta

Research output: Contribution to journalArticlepeer-review

43 Scopus citations

Abstract

Some Abs are more efficacious after being cross-linked to form dimers or multimers, presumably as a result of binding to and clustering more surface target to either amplify or diversify cellular signaling. To improve the therapeutic potency of these types of Abs, we designed and generated Abs that express tandem Fab repeats with the aim of mimicking cross-linked Abs. The versatile design of the system enables the creation of a series of multivalent human IgG Ab forms including tetravalent IgG1, tetravalent F(ab′)2, and linear Fab multimers with either three or four consecutively linked Fabs. The multimerized Abs target the cell surface receptors HER2, death receptor 5, and CD20, and are more efficacious than their parent mAbs in triggering antitumor cellular responses, indicating they could be useful both as reagents for study as well as novel therapeutics.

Original languageEnglish (US)
Pages (from-to)4854-4861
Number of pages8
JournalJournal of Immunology
Volume170
Issue number9
DOIs
StatePublished - May 1 2003

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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