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Related Experiment Video

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High-throughput screening for developability during early-stage antibody discovery using self-interaction

Yuqi Liu1, Isabelle Caffry1, Jiemin Wu2

  • 1Protein Analytics; Adimab; Lebanon, NH USA.

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|February 5, 2014
PubMed
Summary

Developing better monoclonal antibodies (mAbs) is challenging. An improved affinity-capture self-interaction nanoparticle spectroscopy (AC-SINS) assay screens antibody self-association early, improving selection for superior biophysical properties.

Keywords:
aggregationantibody developabilitycross-interactionhigh-throughput screeningnanoparticleself-associationself-interaction

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Area of Science:

  • Biotechnology
  • Protein Engineering
  • Immunology

Background:

  • Monoclonal antibody (mAb) discovery is routine, but developing those with optimal expression, biological activity, and biophysical properties remains challenging.
  • Early assessment of antibody self-association and aggregation is crucial for identifying candidates with superior properties.
  • Existing methods for assessing antibody biophysical properties can be low-throughput.

Purpose of the Study:

  • To report an improved affinity-capture self-interaction nanoparticle spectroscopy (AC-SINS) assay for high-throughput screening of antibody self-association.
  • To enhance the selection process for monoclonal antibodies with superior biophysical characteristics.
  • To provide a more efficient method for identifying promising antibody candidates early in discovery.

Main Methods:

  • Utilized an improved affinity-capture self-interaction nanoparticle spectroscopy (AC-SINS) assay.
  • Employed gold nanoparticles coated with polyclonal capture antibodies to concentrate monoclonal antibodies from dilute solutions.
  • Measured changes in plasmon wavelengths, indicative of mAb self-association, using optical methods.

Main Results:

  • The modified AC-SINS assay demonstrated high throughput screening capabilities for antibody self-association.
  • Measurements from the AC-SINS assay correlated well with established lower-throughput methods like cross-interaction chromatography.
  • The assay is compatible with dilute and unpurified antibody solutions typical in early discovery.

Conclusions:

  • The improved AC-SINS method offers a simple and high-throughput approach for assessing antibody self-interaction.
  • This assay facilitates the early selection of monoclonal antibodies with enhanced biophysical properties.
  • The widespread adoption of this method is expected to improve the overall quality of antibody candidates in discovery pipelines.