Comparative efficiencies of bispecific F(ab′γ)2 and chimeric mouse/human IgG antibodies in recruiting cellular effectors for cytotoxicity via Fcγ receptors

作者: John Greenman , Nancy Hogg , Suzanne Nikoletti , Christopher Slade , George Stevenson

DOI: 10.1007/BF01741745

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摘要: The three forms of Fcγ receptor carried by monocytes (FcγRI, II) and natural killer (NK) cells (FcγRIII) are all capable mediating cell lysis. Here we compare the use F(ab′γ)2 bispecific antibodies, specifically targetting individual FcγR, chimeric IgG mouse/human antibodies which for their ability to mediate target destruction. derivatives prepared linking hinge sulphydryl residues via tandem thioether bonds, using a bismaleimide crosslinker: Fab′ from an anti-FcγR mAb linked common anti-target (BsAb), or mouse antibody human (FabFc bisFabFc). All chick red blood gave efficient lysis, although different effector donors yielded differences in both lytic levels achieved comparative efficiencies derivatives. In contrast, significant lysis guinea pig lymphoblastic leukaemia, L2C, regularly resulted only anti-FcγRIII BsAb These results suggest that chimeric, Fc-containing tumour principally through FcγRIII on NK cells. This is contrast situation with where appear lysing erythrocytes utilizing either cells, because (≈50%) occurred populations magnetically depleted FcγRII FcγRIII. A major difference between these two types derivative was function presence high concentrations normal Fcγ. mediated reactive FcγRI II unaffected at 2.5 mg/ml (a concentration comparable plasma) whereas recognizing were completely inhibited.

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