4.7 Review

Selecting and engineering monoclonal antibodies with drug-like specificity

Journal

CURRENT OPINION IN BIOTECHNOLOGY
Volume 60, Issue -, Pages 119-127

Publisher

ELSEVIER SCI LTD
DOI: 10.1016/j.copbio.2019.01.008

Keywords

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Funding

  1. National Institutes of Health [R01GM104130, R01AG050598]
  2. National Science Foundation [CBET 1513963, 1605266]
  3. Albert M. Mattocks Chair
  4. Directorate For Engineering
  5. Div Of Chem, Bioeng, Env, & Transp Sys [1605266] Funding Source: National Science Foundation

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Despite the recent explosion in the use of monoclonal antibodies (mAbs) as drugs, it remains a significant challenge to generate antibodies with a combination of physicochemical properties that are optimal for therapeutic applications. We argue that one of the most important and underappreciated drug-like antibody properties is high specificity - defined here as low levels of antibody non-specific and self-interactions - which is linked to low off-target binding and slow antibody clearance in vivo and high solubility and low viscosity in vitro. Here, we review the latest advances in characterizing antibody specificity and elucidating its molecular determinants as well as using these findings to improve the selection and engineering of antibodies with extremely high, drug-like specificity.

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