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Targeting malignant B‐cell lymphoma with a humanized anti‐CD22 scFv‐angiogenin immunoenzyme ‡
Author(s) -
Krauss Jürgen,
Arndt Michaela A.E.,
Vu Bang K.,
Newton Dianne L.,
Rybak Susanna M.
Publication year - 2005
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.2005.05356.x
Subject(s) - angiogenin , cd22 , immunotoxin , humanized antibody , microbiology and biotechnology , cytotoxicity , chinese hamster ovary cell , fusion protein , monoclonal antibody , antibody , biology , transfection , cell culture , chemistry , cancer research , recombinant dna , immunology , receptor , biochemistry , in vitro , angiogenesis , gene , genetics
Summary We report on the generation and functional characterization of a humanized immunoenzyme comprising a stable humanized single chain Fv (scFv) with grafted specificity of the anti‐CD22 murine monoclonal antibody RFB4 and the human ribonuclease angiogenin (ANG). The fusion protein produced from transiently transfected mammalian Chinese hamster ovary cells could easily be purified to homogeneity, retained full ribonucleolytic activity, and efficiently killed CD22 + tumour cells with an IC 50 of 56 nmol/l. In contrast, incubation of tumour cells with either ANG or scFv alone did not result in any cytotoxicity. Potent receptor‐mediated killing of target cells, expected lack of extracellular toxicity, predictable low immunogenic potential, and ease of production, suggest that this novel immunoenzyme has potential for the immunotherapy of CD22 + malignancies.