Targeting malignant B-cell lymphoma with a humanized anti-CD22 scFv-angiogenin immunoenzyme.
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.
Krauss
Jürgen
J
SAIC, National Cancer Institute at Frederick, Frederick, MD 21702, USA. juergen.krauss@uni-essen.de
Arndt
Michaela A E
MA
Vu
Bang K
BK
Newton
Dianne L
DL
Rybak
Susanna M
SM
D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D000944:Antigens, Differentiation, B-Lymphocyte / Q000276:immunology; D016466:CHO Cells; D015815:Cell Adhesion Molecules / Q000276:immunology; D045744:Cell Line, Tumor; D006224:Cricetinae; D003601:Cytotoxicity Tests, Immunologic; D005818:Genetic Engineering; D006801:Humans; D007116:Immunization, Passive / Q000379:methods*; D007128:Immunoglobulin Fragments; D037102:Lectins / Q000276:immunology; D016393:Lymphoma, B-Cell / Q000276:immunology / Q000628:therapy*; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use; D012259:Ribonuclease, Pancreatic; D051918:Sialic Acid Binding Ig-like Lectin 2; D014162:Transfection / Q000379:methods
D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; C497867:CD22 protein, human; D015815:Cell Adhesion Molecules; D007128:Immunoglobulin Fragments; D037102:Lectins; D011993:Recombinant Fusion Proteins; D051918:Sialic Acid Binding Ig-like Lectin 2; C046366:angiogenin; D012259:Ribonuclease, Pancreatic