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Effective lysis of lymphoma cells with a stabilised bispecific single-chain Fv antibody against CD19 and FcgammaRIII (CD16).

Abstract：

:A recombinant bispecific single-chain fragment variable antibody (bsscFv), directed against the B-cell antigen CD19 and the low affinity Fc-receptor FcgammaRIII (CD16), was designed for use in the treatment of patients with leukaemias and lymphomas. The Fc-portions of whole antibodies were deliberately eliminated in this construct to avoid undesired effector functions. A stabilised bsscFv, ds[CD19 x CD16], was generated, in which disulphide bonds bridging the respective variable light (VL) and variable heavy (VH) chains were introduced into both component single-chain (sc)Fvs. After production in 293T cells and chromatographic purification, ds[CD19 x CD16] specifically and simultaneously bound both antigens. The serum stability of ds[CD19 x CD16] was increased more than threefold when compared with the unstabilised counterpart, while other biological properties were not affected by these mutations. In antibody-dependent cellular cytotoxicity experiments, ds[CD19 x CD16] mediated specific lysis of both CD19-positive malignant human B-lymphoid cell lines and primary tumour cells from patients with B-cell chronic lymphocytic leukaemia or B-cell acute lymphoblastic leukaemia. Natural killer cells, mononuclear cells (MNCs) from healthy donors and, in some instances, MNCs isolated from patients after allogeneic stem cell transplantation, were used as effectors. Thus, ds[CD19 x CD16] holds promise for the treatment of CD19(+) B-lineage malignancies.

journal_name

Br J Haematol

journal_title

British journal of haematology

authors

Bruenke J,Barbin K,Kunert S,Lang P,Pfeiffer M,Stieglmaier K,Niethammer D,Stockmeyer B,Peipp M,Repp R,Valerius T,Fey GH

doi

10.1111/j.1365-2141.2005.05414.x

subject

Has Abstract

pub_date

2005-07-01 00:00:00

pages

218-28

issue

2

eissn

0007-1048

issn

1365-2141

pii

BJH5414

journal_volume

130

pub_type

杂志文章

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