Human recombinant anti-Rh(D) monoclonal antibodies: improvement of biological properties by in vitro class-switch.
Therapeutic use of human monoclonal antibodies has so far been hampered by their poor availability. Recent developments in recombinant DNA technologies are expected to fill this gap; the variable and constant sequences of antibodies can be selected independently and then subsequently joined to express whole antibodies. We assessed here the potential of this methodology to obtain novel anti-D antibodies with improved biological characteristics. The sequences coding for heavy and light chains of two anti-Rh(D) monoclonal antibodies (one IgG1 and one IgG3) were isolated and co-expressed into murine myeloma cell P3X63.Ag8.653, either directly (parental antibodies) or after exchange of constant heavy chain sequences (class-switched antibodies). Parental antibodies produced either by transfectomas or by hybridomas behaved similarly in analysis of biochemical, binding and effector properties. Class-switched antibodies displayed altered functional properties over parental antibodies. Of particular interest, one of them showed improved phagocytosis potencies over both parental antibodies. Additionally, these results indicate that functional properties do not always simply reflect the addition of properties of constant and variable parts but that interactions between constant and variable regions may interfere.
Klein
P
P
Labaratoire d'Ingénierie Cellulaire et Moléculaire, Lille, France.
Béliard
R
R
Glacet
A
A
Moitel
S
S
Ducrot
T
T
Bourel
D
D
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D000915:Antibody Affinity / Q000276:immunology; D000920:Antibody-Dependent Cell Cytotoxicity / Q000276:immunology; D002460:Cell Line; D003001:Cloning, Molecular; D005822:Genetic Vectors; D006801:Humans; D017578:Immunoglobulin Class Switching; D010587:Phagocytosis / Q000276:immunology; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D011994:Recombinant Proteins