Recombinant human single chain Fv antibodies recognizing human interleukin-6. Specific targeting of cytokine-secreting cells.

The Journal of Biological Chemistry
B KrebsS Rose-John

Abstract

A human antibody library was displayed on the surface of filamentous bacteriophage and screened for binding to human interleukin-6 (IL-6). Two antibody-bearing phages were selected that bound IL-6. The complementary-determining region 3 loops of the variable heavy chains of these two antibodies differed in length and sequence and recognized two distinct epitopes. One of the single chain Fv fragments isolated (H1) was found to bind human (but not murine) IL-6 with an affinity comparable to that of the human IL-6 receptor. H1 also recognized newly synthesized human IL-6 intracellularly, as shown by indirect immunofluorescence. H1 did not neutralize human IL-6, and the H1 epitope was mapped to a region of IL-6 not involved in interactions with IL-6, IL-6 receptor, or the signal-transducing protein gp130. To target IL-6-secreting cells, we then constructed a bispecific antibody fragment (a diabody) comprising H1 and the antigen binding site of the T-cell activating monoclonal antibody OKT3. The diabody led to T-cell-mediated killing of cells secreting IL-6.

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Citations

Dec 28, 1999·Journal of Molecular Recognition : JMR·D G Myszka
Dec 20, 2000·European Journal of Biochemistry·T JostockS Rose-John
Oct 22, 1998·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·B KrebsS Rose-John
Jan 22, 2005·Acta Pharmacologica Sinica·Roland E Kontermann
Jul 5, 2005·Expert Opinion on Investigational Drugs·K J KallenS Rose-John
Aug 30, 2011·Biotechnology Advances·Mohammad Reza SafarnejadStefan Schillberg
Oct 9, 1998·The Journal of Biological Chemistry·C RennéS Rose-John
Jan 5, 2002·The Journal of Biological Chemistry·Akira NakanishiFumio Hanaoka
Jun 9, 2020·Toxicon : Official Journal of the International Society on Toxinology·Lucas B CamposJosé E Barbosa

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