Expression and characterization of a mouse/human chimeric antibody specific for EGF receptor.
Murine antibodies which recognize the epidermal growth factor receptor (EGF-r) are good candidates for therapy and diagnosis of tumors overexpressing this receptor. Here we report the isolation of the variable regions from a murine monoclonal antibody anti-EGF-r (Mint5), the procedure to obtain the mouse/human chimeric antibody (chMint5) and its expression in COS, NS0 and CHO cells. The approach followed to construct chMint5 is based on the use of consensus primers specific for the ends of the variable regions. The sequence imposed by the primers did not affect the targeting potential of the antibody. In fact, the affinity of the chimeric antibody for EGF-r was nearly the same as that of the parental murine antibody. Based on previous in vitro and in vivo animal studies. Mint5 was shown to be a good candidate for the targeting of EGF-r overexpressing tumours. chMint5 is expected to be less immunogenic than murine antibody and therefore, could be useful for human treatment.
Ferrer
C
C
Menarini Ricerche SpA, Department of Biotechnology, Pomezia, Rome, Italy.
Anastasi
A M
AM
Di Massimo
A M
AM
Bullo
A
A
Di Loreto
M
M
Raucci
G
G
Pacilli
A
A
Rotondaro
L
L
Mauro
S
S
Mele
A
A
De Santis
R
R
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis* / Q000235:genetics*; D000915:Antibody Affinity; D000918:Antibody Specificity; D001483:Base Sequence; D019556:COS Cells / Q000276:immunology / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000276:immunology / Q000473:pathology; D000939:Epitopes; D066246:ErbB Receptors / Q000276:immunology*; D005822:Genetic Vectors; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007147:Immunoglobulin Light Chains / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D007142:Immunoglobulin gamma-Chains / Q000235:genetics; D007145:Immunoglobulin kappa-Chains / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D009101:Multiple Myeloma / Q000235:genetics / Q000276:immunology / Q000473:pathology; D011993:Recombinant Fusion Proteins / Q000235:genetics* / Q000276:immunology*; D014162:Transfection; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D000939:Epitopes; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D007135:Immunoglobulin Variable Region; D007142:Immunoglobulin gamma-Chains; D007145:Immunoglobulin kappa-Chains; D011993:Recombinant Fusion Proteins; D066246:ErbB Receptors