Comparison of the inhibition mechanisms of adalimumab and infliximab in treating tumor necrosis factor ?-associated diseases from a molecular view.

ABSTRACT: TNF?-targeting therapy with the use of the drugs Etanercept, Infliximab, and Adalimumab is used in the clinical treatment of various inflammatory and immune diseases. Although all of these reagents function to disrupt the interaction between TNF? and its receptors, clinical investigations showed the advantages of Adalimumab treatment compared with Etanercept and Infliximab. However, the underlying molecular mechanism of action of Adalimumab remains unclear. In our previous work, we presented structural data on how Infliximab binds with the E-F loop of TNF? and functions as a TNF? receptor-binding blocker. To further elucidate the variations between TNF? inhibitors, we solved the crystal structure of TNF? in complex with Adalimumab Fab. The structural observation and the mutagenesis analysis provided direct evidence for identifying the Adalimumab epitope on TNF? and revealed the mechanism of Adalimumab inhibition of TNF? by occupying the TNF? receptor-binding site. The larger antigen-antibody interface in TNF? Adalimumab also provided information at a molecular level for further understanding the clinical advantages of Adalimumab therapy compared with Infliximab.

SUBMITTER: Hu S 

PROVIDER: S-EPMC3779706 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature