A HUMANIZED CD18 ANTIBODY CAN BLOCK FUNCTION WITHOUT CELL DESTRUCTION

Leukocyte integrins are intimately involved in transient adherence of leukocytes to endothelium and to each other in the processes of extrav asation and cell activation. In this study, seven mAb directed against human CD11a and two mAb directed against human CD18, the alpha- and b eta-chains of the leukocyte functional Ag-1 molecule, respectively, we re analyzed for their ability to inhibit several leukocyte' functional Ag-1 -mediated interactions. The best blocking mAb in these studies, a rat anti-human CD18, YFC51.1, was subsequently humanized by compleme ntarily-determining region grafting, associated with human C regions a nd expressed. The humanized mAb was shown to maintain binding for huma n CD18. Even though the humanized mAb was an IgG1 isotype it still ret ained the functional blocking characteristics of the rat mAb while fai ling to mediate cell killing. The IgG1 mAb was unable to bind human Cl q and could block but did not mediate antibody-dependent cellular cyto toxicity.