Efalizumab binding to the LFA-1 α_LI domain blocks ICAM-1 binding via steric hindrance

Integrins as therapeutic targets: lessons and opportunities

“…has been co-crystalized with a number of small molecule inhibitors 131,[140][141][142][143][144][145] identifying the first model of true allosteric inhibition of an α-I domain (FIG. 5b).…”

Structural basis of activation-dependent binding of ligand-mimetic antibody AL-57 to integrin LFA-1

“…A very recent report describes a structure of LFA-1 I domain in complex with the Fab portion of humanized monoclonal IgG 1 antibody, Efalizumab, which is clinically approved drug for treating patients with psoriasis (22). In that structure, Fab binds to the side of the I domain on the ␣1 and ␣3 helices, i.e., to the same epitope as one group of previously mapped competitive antagonist mAbs (18).…”

Host ICAMs play a role in cell invasion by Mycobacterium tuberculosis and Plasmodium falciparum

“…Together, the results show that M5 binds ICAM-1 extracellularly, but bears no effect on the host cell ICAM-1 expression. There are previous reports of disruption of the ICAM-1/LFA-1 interaction using mAbs, ICAM-1 or LFA-1 derived peptides as well as other small molecule inhibitors [51][52][53] , leading to altered immune signalling to control inflammatory and/or autoimmune responses. In case of pathogenic infections, mAb against ICAM-1 as well as soluble ICAM-1 (comprising only the ectodomain) have been previously shown to block Human Rhinovirus infection 54 .…”