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Related Experiment Videos

Engineered antibody Fc variants with enhanced effector function.

Greg A Lazar1, Wei Dang, Sher Karki

  • 1Xencor, Inc., 111 West Lemon Avenue, Monrovia, CA 91016, USA. glazar@xencor.com

Proceedings of the National Academy of Sciences of the United States of America
|March 16, 2006
PubMed
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Engineered antibody Fc regions enhance cancer cell killing via Fcgamma receptors. These optimized variants improve therapeutic antibody efficacy against tumors, even with low antigen levels.

Area of Science:

  • Immunology
  • Biotechnology
  • Oncology

Background:

  • Antibody-dependent cell-mediated cytotoxicity (ADCC) is crucial for monoclonal antibody therapy.
  • Fcgamma receptors (FcγRs) mediate ADCC, balancing activating and inhibitory signals.
  • Optimizing FcγR interactions is key to enhancing therapeutic antibody function.

Purpose of the Study:

  • To engineer novel Fc variants with improved FcγR affinity and specificity.
  • To enhance the in vitro and in vivo effector functions of therapeutic antibodies.
  • To expand the range of antigens targetable by antibody-based cancer therapies.

Main Methods:

  • Utilized computational design algorithms for Fc variant engineering.
  • Employed high-throughput screening to identify optimized Fc variants.

Related Experiment Videos

  • Assessed in vitro effector function and in vivo efficacy in preclinical models.

    • Main Results:

    • Engineered Fc variants demonstrated over a 100-fold increase in in vitro effector function.
    • Achieved significant efficacy against target cells with low antigen expression.
    • Observed enhanced tumor cell killing in a preclinical in vivo model.

    Conclusions:

    • Engineered Fc regions significantly boost antibody-dependent cell-mediated cytotoxicity.
    • These variants improve therapeutic potential for antibody-based cancer treatments.
    • The engineered Fc regions may broaden antigen targets for antibody therapy.