Isolation and characterization of anti-FcgRIII (CD16) llama single-domain antibodies that activate natural killer cells - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Protein Engineering, Design and Selection Année : 2007

Isolation and characterization of anti-FcgRIII (CD16) llama single-domain antibodies that activate natural killer cells

Résumé

FcgRIII (CD16) plays an important role in the anti-tumor effects of therapeutic antibodies. Bi-specific anti-bodies (bsAbs) targeting FcgRIII represent a powerful alternative to the recruitment of the receptor via the Fc fragment, but are not efficiently produced. Single-domain antibodies (sdAbs) endowed with many valuable structural features might help to bypass this problem. In the present work, we have isolated anti-FcgRIII sdAbs (C21 and C28) from a phage library generated from a llama immunized with FcgRIIIB extra-cellular domains. These sdAbs bind FcgRIIIA 1 NK cells and FcgRIIIB 1 poly-morphonuclear cells, but not FcgRI 1 or FcgRII 1 cells, as detected by indirect immunofluorescence. Competition experiments showed that C21 and C28 sdAbs bind different FcgRIII epitopes, with C21 recognizing a linear and C28 a conformational epitope of the receptor. Surface plasmon resonance experiments showed that C21 and C28 sdAbs bind FcgRIII with a K D in the 10 and 80 nM range, respectively. Importantly, the engagement by both molecules of FcgRIIIA expressed by transfected Jurkat T cells or by NK cells derived from peripheral blood induced a strong IL-2 and IFN-g production, respectively. These anti-FcgRIII sdAbs represent versatile tools for generating bsAbs under various formats, able to recruit FcgRIII killer cells to target and destroy tumor cells.
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Dates et versions

hal-02454965 , version 1 (25-01-2020)

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Ghislaine Béhar, Sophie Sibéril, Agnès Groulet, Patrick Chames, Martine Pugnière, et al.. Isolation and characterization of anti-FcgRIII (CD16) llama single-domain antibodies that activate natural killer cells. Protein Engineering, Design and Selection, 2007, 21 (1), pp.1-10. ⟨10.1093/protein/gzm064⟩. ⟨hal-02454965⟩
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