Journal
PROTEIN ENGINEERING DESIGN & SELECTION
Volume 29, Issue 10, Pages 419-426Publisher
OXFORD UNIV PRESS
DOI: 10.1093/protein/gzw024
Keywords
antibody; cetuximab; computational protein design; humanization; thermostability
Funding
- National Institute of General Medical Sciences at the National Institutes of Health [R01 GM098977]
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Humanization reduces the immunogenicity risk of therapeutic antibodies of non-human origin. Thermostabilization can be critical for clinical development and application of therapeutic antibodies. Here, we show that the computational antibody redesign method Computationally Driven Antibody Humanization (CoDAH) enables these two goals to be accomplished simultaneously and seamlessly. A panel of CoDAH designs for the murine parent of cetuximab, a chimeric anti-EGFR antibody, exhibited both substantially improved thermostabilities and substantially higher levels of humanness, while retaining binding activity near the parental level. The consistently high quality of the turnkey CoDAH designs, over a whole panel of variants, suggests that the computationally directed approach encapsulates key determinants of antibody structure and function.
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