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Review ArticleR

The Intriguing Options of Multispecific Antibody Formats for Treatment of Cancer

ULRICH H. WEIDLE, GEORG TIEFENTHALER, ELISABETH H. WEISS, GUY GEORGES and ULRICH BRINKMANN
Cancer Genomics & Proteomics January 2013, 10 (1) 1-18;
ULRICH H. WEIDLE
1 Roche Pharma Research and Early Development, Roche Diagnostics GmbH, Penzberg, Germany
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GEORG TIEFENTHALER
1 Roche Pharma Research and Early Development, Roche Diagnostics GmbH, Penzberg, Germany
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ELISABETH H. WEISS
2 Department of Biology II, Ludwig Maximilian University, Munich, Germany
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GUY GEORGES
1 Roche Pharma Research and Early Development, Roche Diagnostics GmbH, Penzberg, Germany
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ULRICH BRINKMANN
1 Roche Pharma Research and Early Development, Roche Diagnostics GmbH, Penzberg, Germany
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Abstract

The advent of various technologies for the generation of bi- and multispecific recombinant antibody-based molecules brought with it a multitude of formats for selecting target combinations. Some of the format options are outlined from a technical point of view. We focus on the achievements and prospects of the underlying technologies for generating bi- and multispecific antibodies to i) target immune effector cells and/or cytokines to tumors, ii) engage death receptors on tumor cells simultaneously, iii) improve antiangiogenic intervention by blocking complementary pathways of angiogenesis and iv) achieve more efficient targeting of human epidermal growth factor-related and other receptor tyrosine kinase-related pathways. Many of the outlined approaches, in addition to potential improvement of therapeutic efficacy in comparison to single agent intervention, also offer the potential to counteract therapy resistance.

  • Antibody formats
  • cytokine delivery
  • death receptors
  • HER signaling
  • recruitment of immune effector cells
  • inhibition of angiogenesis
  • review
  • Received December 21, 2012.
  • Revision received January 23, 2013.
  • Accepted January 23, 2013.
  • Copyright© 2013 International Institute of Anticancer Research (Dr. John G. Delinasios), All rights reserved
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Cancer Genomics - Proteomics: 10 (1)
Cancer Genomics & Proteomics
Vol. 10, Issue 1
January-February 2013
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The Intriguing Options of Multispecific Antibody Formats for Treatment of Cancer
ULRICH H. WEIDLE, GEORG TIEFENTHALER, ELISABETH H. WEISS, GUY GEORGES, ULRICH BRINKMANN
Cancer Genomics & Proteomics Jan 2013, 10 (1) 1-18;

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The Intriguing Options of Multispecific Antibody Formats for Treatment of Cancer
ULRICH H. WEIDLE, GEORG TIEFENTHALER, ELISABETH H. WEISS, GUY GEORGES, ULRICH BRINKMANN
Cancer Genomics & Proteomics Jan 2013, 10 (1) 1-18;
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  • Article
    • Abstract
    • Formats
    • Initial Efforts to Recruit Immune Effector Cells Using Bispecific Antibodies
    • Targeting CD28 for Recruitment of Immune Effector Cells
    • Trifunctional Bispecific Antibodies
    • Bipecific T-Cell Engagers (BiTEs)
    • Further Formats for Recruitment of Immune Effector Cells
    • Single-chain Triple Antibodies
    • Cytotoxic Bispecific Antibodies
    • Bispecific Antibodies Directed against Receptor-tyrosine Kinases
    • Bispecific Antibodies Interfering with Tumor Angiogenesis
    • Bispecific Antibodies for Targeting of Intracellular Antigens
    • Conclusion
    • References
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Keywords

  • Antibody formats
  • cytokine delivery
  • death receptors
  • HER signaling
  • recruitment of immune effector cells
  • inhibition of angiogenesis
  • review
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