Expression and characterization of a mouse/human chimeric antibody specific for EGF receptor

• Published in: Journal of biotechnology 1996-11, Vol.52 (1), p.51-60
• Main Authors: Ferrer, Cristina, Anastasi, Anna M., Di Massimo, Anna M., Bullo, Angela, Di Loreto, Mario, Raucci, Giuseppe, Pacilli, Aurelio, Rotondaro, Luigi, Mauro, Sandro, Mele, Antonio, De Santis, Rita
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Antibodies, Monoclonal - biosynthesis; Antibodies, Monoclonal - genetics; Antibody Affinity; Antibody Specificity; Base Sequence; Biological and medical sciences; Biotechnology; Carcinoma, Squamous Cell - immunology; Carcinoma, Squamous Cell - pathology; Chimeric antibody; COS Cells - immunology; COS Cells - metabolism; EGF-receptor; Epitopes; Fundamental and applied biological sciences. Psychology; Genetic Vectors; Health. Pharmaceutical industry; Humans; Immunoglobulin gamma-Chains - genetics; Immunoglobulin Heavy Chains - genetics; Immunoglobulin humanization; Immunoglobulin kappa-Chains - genetics; Immunoglobulin Light Chains - genetics; Immunoglobulin Variable Region - genetics; Immunological technics applied to diagnosis; Industrial applications and implications. Economical aspects; Mice; Molecular Sequence Data; Multiple Myeloma - genetics; Multiple Myeloma - immunology; Multiple Myeloma - pathology; Receptor, Epidermal Growth Factor - immunology; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - immunology; Transfection; Tumor Cells, Cultured
• ISSN: 0168-1656; 1873-4863
• DOI: 10.1016/S0168-1656(96)01625-2

Murine antibodies which recognize the epidermal growth factor receptor (EGF-r) are good candidates for therapy and diagnosis of tumours 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.