Production of Human Monoclonal Antibodies in SCID Mouse

• Published in: MICROBIOLOGY and IMMUNOLOGY 1997, Vol.41(12), pp.901-907
• Main Authors: Nguyen, Hai, Sandhu, Jasbir, Hozumi, Nobumichi
• Format: Article
• Language: English
• Subjects: Animals; Antibodies, Monoclonal - biosynthesis; Antibodies, Monoclonal - genetics; Antibodies, Monoclonal - immunology; Antibodies, Monoclonal - isolation & purification; Antibody Affinity; Antibody maturation; Antigens - immunology; Bacteriophages; Biological and medical sciences; Biotechnology; Fundamental and applied biological sciences. Psychology; Health. Pharmaceutical industry; Human lymphocytes; Human self antigen; Humans; Immunoglobulin Fragments - biosynthesis; Immunoglobulin Fragments - immunology; Immunotherapy; Industrial applications and implications. Economical aspects; Lymphocyte Transfusion; Mice; Mice, SCID - genetics; Mice, SCID - immunology; Monoclonal antibodies; Peptide Library; Phage display library; Production of active biomolecules; Respiratory syncytial virus; Transplantation, Heterologous
• ISSN: 0385-5600; 1348-0421
• DOI: 10.1111/j.1348-0421.1997.tb01948.x

The advent of hybridoma technology for the production of mouse monoclonal antibodies (MoMAbs) has made it possible to obtain large quantities of antibodies with defined antigen specificity (26). Since then, antibody immunotherapy has become a reality. However, actual clinical application, particularly for therapeutic purposes, has been hampered by the immunogenicity of MoMAbs, known as human anti-mouse antibody (HAMA) response (20). To solve this problem, several antibody engineering techniques have been developed to generate MAbs more suitable for clinical use. These methods include the construction of mouse/human chimeric Abs (7) and humanized MoMAbs (45). However, these antibody engineering methods are laborious and costly. Human monoclonal antibodies (HuMAbs) would be ideal for clinical purposes. Thus, the development of an efficient method to generate HuMAbs with high affinity would be a significant advance in the fields of biotechnology and medicine. We have recently developed a very efficient method to engraft human peripheral blood lymphocytes (Hu-PBL) in severe combined immunodeficient (SCID) mouse (43). The human immune response could be optimized in the Hu-PBL-SCID mouse model, and human antibodies of desired specificity could be generated. In this review we describe a method to obtain HuMAbs with high antigen binding affinity by optimizing the human immune response to specific antigens in the Hu-PBL-SCID mouse model.