Review Myeloma expression systems Esther M. Yoo, Koteswara R. Chintalacharuvu, Manuel L. Penichet, Sherie L. Morrison * Department of Microbiology, Immunology and Molecular Genetics and the Molecular Biology Institute, University of California Los Angeles, 611 S. Charles Young Drive, Los Angeles, CA 90095, USA Received 26 October 2001; accepted 26 October 2001 Abstract Myeloma expression systems have been utilized successfully for the production of various recombinant proteins. In particular, myeloma cell lines have been exploited to express a variety of different antibodies for diagnostic applications as well as in the treatment of various human diseases. The use of myeloma cells for antibody production is advantageous because they are professional immunoglobulin-secreting cells and are able to make proper post-translational modifications. Proper glycosylation has been shown to be important for antibody function. Advances in genetic engineering and molecular biology techniques have made it possible to isolate murine and human variable regions of almost any desired specificity. Antibodies and antibody variants produced in myeloma cells have been extremely helpful in elucidating the amino acid residues and structural motifs that contribute to antibody function. Because of their domain nature, immunoglobulin genes can be easily manipulated to produce chimeric or humanized antibodies. These antibodies are less immunogenic in humans and also retain their specificity for antigen and biologic properties. In addition, novel proteins in which antibodies are fused to non-immunoglobulin sequences as well as secretory IgA have been produced in myeloma cells. D 2002 Elsevier Science B.V. All rights reserved. Keywords: Myeloma cells; Monoclonal antibodies; Antibody engineering; Protein expression 0022-1759/02/$ - see front matter D 2002 Elsevier Science B.V. All rights reserved. PII:S0022-1759(01)00559-2 Abbreviations: Ab, antibody; ADCC, antibody-dependent cell-mediated cytotoxicity; ASGR, asialoglycoprotein-binding receptor; Av, avidin; BBB, blood–brain barrier; CDC, complement-dependent cytotoxicity; CHO, Chinese hamster ovary cells; CMV, cytomegalovirus; C region, constant region; dhfr, dihydrofolate reductase; FcR, Fc receptor; GlcNAc, N-acetylglucosamine; GM-CSF, granulocyte- macrophage colony-stimulating factor; gs, glutamine synthetase; H chain, heavy chain; HPRT, hypoxanthine-guanine phosphoribosyl transferase; Id, idiotype; ID, injected dose; Ig, immunoglobulin; IGF, insulin-like growth factor; IL, interleukin; L chain, light chain; MAbs, monoclonal antibodies; MBP, mannose binding protein; NeuGc, N-glycolylneuramic acid; NeuAc, N-acetylneuraminic acid; pIgA, polymeric IgA; pIgR, poly-immunoglobulin receptor; PCR, polymerase chain reaction; PNA, peptide-nucleic acid; SC, secretory component; sIgA, secretory IgA; TAA, tumor associated antigen; Tf, transferrin; TfR, transferrin receptor; V region, variable region. * Corresponding author. Tel.: +1-310-206-5127; fax: +1-310-206-7286. E-mail address: sheriem@microbio.ucla.edu (S.L. Morrison). www.elsevier.com/locate/jim Journal of Immunological Methods 261 (2002) 1 – 20