Abstract
Since the first monoclonal antibody, muromonab-CD3, was approved for therapeutic use in 1986, numerous molecules have been targeted using therapeutic antibody technology, resulting in 26 therapeutic antibodies being approved by the US FDA as of November, 2009. Initial concerns regarding antibody drugs focused on immunogenicity, short serum half-life, and weak efficacy. As the types of antibodies progressed from murine to chimeric, humanized, and fully human antibodies, great progress has been made in immunogenicity and in vivo instability issues. For example, humanized antibodies, such as bevacizumab, exhibit less than 0.2% immunogenicity and a 20 day serum half-life, which is comparable to native immunoglobulin. Some recently developed antibodies are exceedingly efficacious and have become first-line therapy for their target diseases. Here, we address and analyze all clinically approved therapeutic antibodies to date by discussing immunogenicity, half-life, and efficacy.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Swann, P. G., M. Tolnay, S. Muthukkumar, M. A. Shapiro, B. L. Rellahan, and K. A. Clouse (2008) Considerations for the development of therapeutic monoclonal antibodies. Curr. Opinion Immunol. 20: 493–499.
Norman, D. J., L. Chatenoud, D. Cohen, M. Goldman, and C. F. Shield (1993) Consensus statement regarding OKT3-induced cytokine-release syndrome and human antimouse antibodies. Transplant. Proc. 25: 89–92.
Ledermann, J. A., R. H. J. Begent, K. D. Bagshawe, S. J. Riggs, F. Searle, M. G. Glaser, A. J. Green, and R. G. Dale (1988) Repeated antitumour antibody therapy in man with suppression of the host response by cyclosporine-A. British Jl Cancer 58: 654–657.
Leitha, T., R. Walter, W. Schlick, and R. Dudczak (1991) TC-99M-anti-CEA radioimmunoscintigraphy of lung adenocarcinoma. Chest 99: 14–19.
Riva, P., M. Marangolo, S. Lazzari, M. Agostini, G. Sarti, G. Moscatelli, G. Franceschi, A. Spinelli, and G. Vecchietti (1989) Locoregional immunotherapy of human ovarian-cancer-preliminary-results. Nuclear Med. Biol. 16: 659–666.
Mellstedt, H. (1992) The clinical significance of HAMA in patients treated with mouse monoclonal antibodies. Cell biophys. 21: 153–165.
Kuusreichel, K., L. S. Grauer, L. M. Karavodin, C. Knott, M. Krusemeier, and N. E. Kay (1994) Will immunogenicity limit the use, efficacy, and future-development of the therapeutic monoclonal antibodies? Clin. Diagn. Lab. Immunol. 1: 365–372.
Biogen IDEC (2002) Zevalin full prescribing information.
Kaminski, M. S., A. D. Zelenetz, O. W. Press, M. Saleh, J. Leonard, L. Fehrenbacher, T. A. Lister, R. J. Stagg, G. F. Tidmarsh, S. Kroll, R. L. Wahl, S. J. Knox, and J. M. Vose (2001) Pivotal study of iodine I 131 Tositumomab for chemotherapy-refractory low-grade or transformed low-grade B-cell non-Hodgkin’s lymphomas. J. Clin. Oncol. 19: 3918–3928.
Hwang, W. Y. K. and J. Foote (2005) Immunogenicity of engineered antibodies. Methods 36: 3–10.
Tcheng, J. E., D. J. Kereiakes, A. M. Lincoff, B. S. George, N. S. Kleiman, D. C. Sane, D. B. Cines, R. E. Jordan, M. A. Mascelli, M. A. Langrall, L. Damaraju, A. Schantz, M. B. Effron, and G. A. Braden (2001) Abciximab readministration: Results of the ReoPro readministration registry. Circulation 104: 870–875.
Genentech (1997) Rituxan full prescribing information.
Novartis (1998) Simulect full prescribing information.
Centocor (1998) Remicade full prescribing information.
Imclone Systems (2004) Erbitux full prescribing information.
Protein Design Lab (1997) Zenapax full prescribing information.
Medimmune (1998) Synagis full prescribing information.
Genentech (1998) Herceptin full prescribing information.
Wyeth (2000) Mylotarg full prescribing information.
Millenium/LEX (2001) Campath full prescribing information.
Genentech (2003) Xolair full prescribing information.
Genentech (2003) Raptiva full prescribing information.
Imclone Systems (2004) Avastin full prescribing information.
Biogen IDEC (2004) Tysabri full prescribing information.
Genentech (2006) Lucentis full prescribing information.
Alexion Pharmaceuticals (2007) Soliris full prescribing information.
UCB (2008) Cimzia full prescribing information.
Lichtenstein, G. R., J. F. Colombel, R. Bloomfield, and W. J. Sandborn (2008) Long-term safety of an anti-TNF drug by duration of exposure compared to non-anti-TNF exposed patients with Crohn’s disease: Novel data from the certolizumab pegol development program. Gastroenterol. 134: 68.
Rivkin, A. (2009) Certolizumab Pegol for the Management of Crohn’s Disease in Adults. Clin. Therapeutics. 31: 1158–1176.
Genentech (Roche) (2010) Actemra prescribing information.
Abbott (2002) Humira full prescribing information.
Amgen (2006) Vectibix full prescribing information.
Centocor (2009) Simponi full prescribing information.
Novartis (2009) Ilaris full prescribing information.
GlaxoSmithKline (2009) Arzerra full prescribing information.
Roopenian, D. C. and S. Akilesh (2007) FcRn: the neonatal Fc receptor comes of age. Nature Rev. Immunol. 7: 715–725.
Kacskovics, I., Z. Kis, B. Mayer, A. P. West, N. E. Tiangco, M. Tilahun, L. Cervenak, P. J. Bjorkman, R. A. Goldsby, O. Szenci, and L. Hammarstrom (2006) FcRn mediates elongated serum half-life of human IgG in cattle. Int. Immunol. 18: 525–536.
Thurmann, P. and S. Harder (1996) Criteria for the appropriate drug utilisation of immunoglobulin. Pharmacoeconomics 9: 417–429.
Wang, D., C. Cummins, S. Bayliss, J. Sandercock, and A. Burls (2008) Immunoprophylaxis against respiratory syncytial virus (RSV) with palivizumab in children: A systematic review and economic evaluation. Health Technol. Assessment 12: 1–86.
Hillmen, P., N. S. Young, J. Schubert, R. A. Brodsky, G. Socie, P. Muus, A. Roth, J. Szer, M. O. Elebute, R. Nakamura, P. Browne, A. M. Risitano, A. Hill, H. Schrezenmeier, C. Fu, J. Maciejewski, S. A. Rollins, C. F. Mojcik, R. P. Rother, and L. Luzzatto (2006) The complement inhibitor eculizumab in paroxysmal nocturnal hemoglobinuria. N. Engl. J. Med. 355: 1233–1243.
Lachmann, H. J., I. Kone-Paut, J. B. Kuemmerle-Deschner, K. S. Leslie, E. Hachulla, P. Quartier, X. Gitton, A. Widmer, N. Patel, P. N. Hawkins, and C. S. G. Canakinumab (2009) Use of Canakinumab in the Cryopyrin-Associated Periodic Syndrome. N. Eng. J.Med. 360: 2416–2425.
Witzig, T. E., C. A. White, L. I. Gordon, G. A. Wiseman, C. Emmanouilides, J. L. Murray, J. Lister, and P. S. Multani (2003) Safety of yttrium-90 ibritumomab tiuxetan radioimmunotherapy for relapsed low-grade, follicular, or transformed non-Hodgkin’s lymphoma. J. Clin. Oncol. 21: 1263–1270.
Witzig, T. E., I. W. Flinn, L. I. Gordon, C. Emmanouilides, M. S. Czuczman, M. N. Saleh, L. Cripe, G. Wiseman, T. Olejnik, P. S. Multani, and C. A. White (2002) Treatment with ibritumomab tiuxetan radioimmunotherapy in patients with rituximab-refractory follicular non-Hodgkin’s lymphoma. J. Clin. Oncol. 20: 3262–3269.
Thienelt, C. D., P. A. Bunn, N. Hanna, A. Rosenberg, M. N. Needle, M. E. Long, D. L. Gustafson, and K. Kelly (2005) Multicenter phase I/II study of cetuximab with paclitaxel and carboplatin in untreated patients with stage IV non-small-cell lung cancer. J. Clin. Oncol. 23: 8786–8793.
Saltz, L. B., N. J. Meropol, P. J. Loehrer, M. N. Needle, J. Kopit, and R. J. Mayer (2004) Phase II trial of cetuximab in patients with refractory colorectal cancer that expresses the epidermal growth factor receptor. J. Clin. Oncol. 22: 1201–1208.
Humblet, Y., E. Vega-Villegas, R. Mesia, A. Awada, L. Geoffrois, C. Borel, R. Hitt, N. Amellal, E. H. Bessa, and J. Bourhis (2006) Phase I study of cetuximab in combination with cisplatin or carboplatin and 5-fluorouracil (5-FU) in patients (pts) with recurrent and/or metastatic squamous cell carcinoma of the head and neck (SCCHN). J. Clin. Oncol. 24 (18): 2866–2872.
Martinelli, E., R. De Palma, M. Orditura, F. De Vita, and F. Ciardiello (2009) Anti-epidermal growth factor receptor monoclonal antibodies in cancer therapy. Clin. Exp. Immunol. 158: 1–9.
EMEA (2009) Summary of product characteristics.
American Society of Clinical Oncology (ASCO) 45th Annual Meeting (2009) poster No.1017.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Yoon, S., Kim, YS., Shim, H. et al. Current perspectives on therapeutic antibodies. Biotechnol Bioproc E 15, 709–715 (2010). https://doi.org/10.1007/s12257-009-3113-1
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12257-009-3113-1