Engineering antibody Fv fragments for cancer detection and therapy: disulfide-stabilized Fv fragments.
Disulfide-stabilized Fv fragments of antibodies (dsFv) are molecules in which the VH-VL heterodimer is stabilized by an interchain disulfide bond engineered between structurally conserved framework positions distant from complementarity-determining regions (CDRs). This method of stabilization is applicable for the stabilization of many antibody Fvs and has also been applied to a T-cell receptor Fv. A summary of the design strategy, and the construction and production of various dsFvs and dsFv-fusion proteins is presented. Included in the discussion are the biochemical features of dsFvs in comparison with scFvs, the effect of disulfide stabilization on Fv binding and activity, and various applications of dsFvs and dsFv-immunotoxins for tumor imaging and the treatment of solid tumors in animal models.
Reiter
Y
Y
Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4255, USA.
Brinkmann
U
U
Lee
B
B
Pastan
I
I
D000818:Animals; D001435:Bacteriophages / Q000235:genetics / Q000276:immunology; D001709:Biotechnology; D004220:Disulfides / Q000737:chemistry; D015195:Drug Design; D004355:Drug Stability; D006801:Humans; D007128:Immunoglobulin Fragments / Q000737:chemistry / Q000627:therapeutic use*; D007135:Immunoglobulin Variable Region / Q000737:chemistry / Q000627:therapeutic use*; D007159:Immunologic Tests; D007167:Immunotherapy; D000922:Immunotoxins / Q000737:chemistry / Q000627:therapeutic use; D008958:Models, Molecular; D009369:Neoplasms / Q000175:diagnosis* / Q000628:therapy*; D011355:Prodrugs / Q000627:therapeutic use; D011487:Protein Conformation; D015202:Protein Engineering; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology; D011994:Recombinant Proteins / Q000737:chemistry / Q000627:therapeutic use
D004220:Disulfides; D007128:Immunoglobulin Fragments; D007135:Immunoglobulin Variable Region; D000922:Immunotoxins; D011355:Prodrugs; D011948:Receptors, Antigen, T-Cell; D011994:Recombinant Proteins; C055966:immunoglobulin Fv