A recombinant, fully human monoclonal antibody with antitumor activity constructed from phage-displayed antibody fragments.
A single-chain Fv antibody fragment specific for the tumor-associated Ep-CAM molecule was isolated from a semisynthetic phage display library and converted into an intact, fully human IgG1 monoclonal antibody (huMab). The purified huMab had an affinity of 5 nM and effectively mediated tumor cell killing in in vitro and in vivo assays. These experiments show that nonimmunized phage antibody display libraries can be used to obtain high-affinity, functional, and clinically applicable huMabs directed against a tumor-associated antigen.
Huls
G A
GA
Department of Immunology, University Hospital Utrecht, The Netherlands.
Heijnen
I A
IA
Cuomo
M E
ME
Koningsberger
J C
JC
Wiegman
L
L
Boel
E
E
van der Vuurst de Vries
A R
AR
Loyson
S A
SA
Helfrich
W
W
van Berge Henegouwen
G P
GP
van Meijer
M
M
de Kruif
J
J
Logtenberg
T
T
D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry* / Q000627:therapeutic use; D000951:Antigens, Neoplasm / Q000276:immunology*; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000627:therapeutic use; D001435:Bacteriophages / Q000235:genetics; D015153:Blotting, Western; D015815:Cell Adhesion Molecules / Q000276:immunology*; D002452:Cell Count; D003110:Colonic Neoplasms / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D000071858:Epithelial Cell Adhesion Molecule; D005434:Flow Cytometry; D015723:Gene Library; D016179:Granulocyte Colony-Stimulating Factor / Q000378:metabolism; D006801:Humans; D007128:Immunoglobulin Fragments / Q000737:chemistry*; D007150:Immunohistochemistry; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008967:Molecular Biology / Q000379:methods*; D009504:Neutrophils / Q000187:drug effects; D011994:Recombinant Proteins / Q000737:chemistry / Q000627:therapeutic use; D013997:Time Factors; D014162:Transfection; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D015815:Cell Adhesion Molecules; D000071858:Epithelial Cell Adhesion Molecule; D007128:Immunoglobulin Fragments; D011994:Recombinant Proteins; C055966:immunoglobulin Fv; D016179:Granulocyte Colony-Stimulating Factor