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  • Oral presentation
  • Open Access

Rational engineering of Fc/Fc receptor interactions to improve antibody potency

  • 1,
  • 1 and
  • 1
Breast Cancer Research20035 (Suppl 1) :59

https://doi.org/10.1186/bcr718

  • Published:

Keywords

  • Effector Function
  • Design Automation
  • Polymorphic Form
  • Gamma Receptor
  • Rational Engineering

Despite the growing clinical application of monoclonal antibodies as anti-cancer therapeutics, their ability to destroy targeted tumor cells is suboptimal. We have leveraged our Protein Design Automation® technology to engineer antibodies with greater tumor killing power by augmenting the capacity of the Fc region to interact with the Fc gamma receptors (FcγRs) that mediate cytotoxic effector functions. A panel of Fc variants has been generated that display substantial enhancements over existing variants in both in vitro Fc/FcγR binding assays and cell-based ADCC assays. Our most promising candidates have been validated in the context of three approved anti-cancer antibodies, and characterized with regard to their specificity for activation versus inhibitory receptors, and their affinity for clinically relevant polymorphic forms of FcγRIIIa.

Authors’ Affiliations

(1)
Xencor, Monrovia, California, USA

Copyright

© BioMed Central 2003

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