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Aspects of Isotype Selection

  • Zehra KaymakcalanEmail author
  • Alexander Ibraghimov
  • Andrew G. Goodearl
  • Jochen G. Salfeld
Protocol
Part of the Springer Protocols Handbooks book series (SPH)

The history of isotype selection for therapeutic antibodies clearly demonstrates that solid understanding of the biologic effects mediated by immunoglobulin (Ig) subclasses IgG1, IgG2, IgG3, and IgG4 and their variants is a prerequisite for optimal antibody development. The choices of isotype-constant regions for full-length antibody generation are becoming more complex by the availability of engineered variants and, in some cases, mixed isotypes. This review focuses on important lessons from preclinical studies, and clinical trials, which underscore that careful selection of isotypes is critical given their differential effects on antibody function. The molecular requirements vary for different mechanisms of action of therapeutic antibodies (eg, neutralizing, agonistic, conjugated), and IgG properties beneficial for one mechanism might be detrimental for another. Key isotype selection principles for optimal antibody development are reviewed, and case studies are discussed.

Keywords

Effector Function Cell Depletion Constant Region IgG1 Isotype Therapeutic Antibody 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgements

Editorial support was provided by Robin L. Stromberg, PhD, of Arbor Communications, Inc. (Ann Arbor, MI, USA) and funded by Abbott Laboratories.

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Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Zehra Kaymakcalan
    • 1
    Email author
  • Alexander Ibraghimov
    • 1
  • Andrew G. Goodearl
    • 1
  • Jochen G. Salfeld
    • 1
  1. 1.Department of BiologicsAbbott Bioresearch CenterWorcesterUSA

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