Affinity-matured variants derived from nimotuzumab keep the original fine specificity and exhibit superior biological activity.

ABSTRACT: Nimotuzumab is a humanized monoclonal antibody against the Epidermal Growth Factor Receptor with a long history of therapeutic use, recognizing an epitope different from the ones targeted by other antibodies against the same antigen. It is also distinguished by much less toxicity resulting in a better safety profile, which has been attributed to its lower affinity compared to these other antibodies. Nevertheless, the ideal affinity window for optimizing the balance between anti-tumor activity and toxic effects has not been determined. In the current work, the paratope of the phage-displayed nimotuzumab Fab fragment was evolved in vitro to obtain affinity-matured variants. Soft-randomization of heavy chain variable region CDRs and phage selection resulted in mutated variants with improved b

SUBMITTER: Tundidor Y 

PROVIDER: S-EPMC6985160 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature