Structural insights into humanization of anti-tissue factor antibody 10H10.

ABSTRACT: Murine antibody 10H10 raised against human tissue factor is unique in that it blocks the signaling pathway, and thus inhibits angiogenesis and tumor growth without interfering with coagulation. As a potential therapeutic, the antibody was humanized in a two-step procedure. Antigen-binding loops were grafted onto selected human frameworks and the resulting chimeric antibody was subjected to affinity maturation by using phage display libraries. The results of humanization were analyzed from the structural perspective through comparison of the structure of a humanized variant with the parental mouse antibody. This analysis revealed several hot spots in the framework region that appear to affect antigen binding, and therefore should be considered in human germline selection. In addition, some

SUBMITTER: Teplyakov A 

PROVIDER: S-EPMC5825201 | biostudies-literature | 2018 Feb/Mar

REPOSITORIES: biostudies-literature