Abstract
Based on his observations from selective histological staining of bacteria, Paul Ehrlich in 1900 published his idea that certain compounds could be used as “magic bullets” to selectively target external pathogens or even tumours (Ehrlich 1900). With the description of the hybridoma technology by Köhler and Milstein in 1975, the production of targeted monoclonal antibodies (mAbs) became possible and Paul Ehrlich’s dream of magic bullets a reality. Currently, more than a dozen mAbs are licensed (Reichert et al. 2005), and more promising products are about to enter clinical development. While the first antibodies were of completely murine origin due to the underlying technology, scientists started an “evolution” of mAbs in order to reduce immunogenicity (Borchmann et al. 2001). Murine proteins are highly immunogenic, and continuous use in humans in most cases is not possible due to the occurrence of neutralizing antibodies, leading to loss of efficacy and/or safety problems like infusion reactions. Therefore, chimaeric antibodies such as infliximab (Remicade) were developed, reducing immunogenicity by replacement of the murine Fc part by the human counterpart.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Astrom KE, Mancall EL, Richardson EP, Jr (1958) Progressive multifocal leuko-encephalopathy: a hitherto unrecognized complication of chronic lymphatic leukaemia and Hodgkin’s disease. Brain 81:93–111
Baron JL, Madri JA, Ruddle NH, Hashim G, Janeway CA, Jr (1993) Surface expression of alpha 4 integrin by CD4 T cells is required for their entry into brain parenchyma. J ExpMed 177(1):57–68
Beutler BA (1999) The role of tumor necrosis factor in health and disease. J Rheumatol Suppl 57:16–21
Borchmann P, Riethmuller G, Engert A (2001) [Monoclonal antibodies: development and clinical prospects] [in German]. Internist (Berl) 42(6):803–4, 807–814
Crone SA, Zhao YY, Fan L, Gu Y, Minamisawa S, Liu Y, Peterson KL, Chen J, Kahn R, Condorelli G, Ross J, Jr, Chien KR, Lee KF (2002) ErbB2 is essential in the prevention of dilated cardiomyopathy. Nat Med 8(5):459–465
Ehrlich P (1900) On immunity with special reference to cell life. Proc R Soc 66:424–448
European Medicines Agency (2006a) Remicade European Public Assessment Report. EMEA, London. http://www.emea.europa.eu/humandocs/Humans/EPAR/remicade/remicade.htm
European Medicines Agency (2006b) Tysabri European Public Assessment Report. EMEA, London. http://www.emea.europa.eu/humandocs/Humans/EPAR/tysabri/tysabri.htm
European Medicines Agency (2006c) Herceptin European Public Assessment Report. EMEA, London. http://www.emea.europa.eu/humandocs/Humans/EPAR/herceptin/herceptin.htm
Ewer MS, Vooletich MT, Durand JB, Woods ML, Davis JR, Valero V, Lenihan DJ (2005) Reversibility of trastuzumab-related cardiotoxicity: new insights based on clinical course and response to medical treatment. J Clin Oncol 23(31):7820–7826
Gold R, Hohlfeld R (2007) Multiple sclerosis: new immunobiologics. In: Boehncke W-H, Radeke HH (eds) Biologics in general medicine, Chapter 13. Springer-Verlag, Heidelberg [this volume]
Hynes RO (2002) Integrins: bidirectional, allosteric signaling machines. Cell 110(6):673–687
Kleinschmidt-DeMasters BK, Tyler KL (2005) Progressive multifocal leukoencephalopathy complicating treatment with natalizumab and interferon beta-1a for multiple sclerosis. N Engl J Med 353(4):369–374
Köhler G, Milstein C (1975) Continuous cultures of fused cells secreting antibody of predefined specificity. Nature 256(5517):495–497
Langer-Gould A, Atlas SW, Green AJ, Bollen AW, Pelletier D (2005) Progressive multifocal leukoencephalopathy in a patient treated with natalizumab. N Engl J Med 353(4):375–381
Lobb RR, Hemler ME (1994) The pathophysiologic role of alpha 4 integrins in vivo. J Clin Invest 94(5):1722–1728
Luhder F, Huang Y, Dennehy KM, Guntermann C, Muller I, Winkler E, Kerkau T, Ikemizu S, Davis SJ, Hanke T, Hunig T (2003) Topological requirements and signaling properties of T cell-activating, anti-CD28 antibody superagonists. J Exp Med 197(8):955–966
Miller DH, Khan OA, Sheremata WA, Blumhardt LD, Rice GP, Libonati MA, Willmer-Hulme AJ, Dalton CM, Miszkiel KA, O’Connor PW; International Natalizumab Multiple Sclerosis Trial Group (2003) A controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med 348(1):15–23
Olayioye MA, Neve RM, Lane HA, Hynes NE (2000) The ErbB signaling network: receptor heterodimerization in development and cancer. EMBO J 19:3159–3167
Polman CH, O’Connor PW, Havrdova E, Hutchinson M, Kappos L, Miller DH, Phillips JT, Lublin FD, Giovannoni G, Wajgt A, Toal M, Lynn F, Panzara MA, Sandrock AW; AFFIRM Investigators (2006) A randomized, placebo-con-trolled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med 354(9):899–910
Reichert JM, Rosensweig CJ, Faden LB, Dewitz MC (2005) Monoclonal antibody successes in the clinic. Nat Biotechnol 23(9):1073–1078
Salfeld J, Kupper H (2007) Adalimumab. In: Boehncke W-H, Radeke HH (eds) Biologics in general medicine, Chapter 3. Springer-Verlag, Heidelberg [this volume]
Schneider CK, Kalinke U, Löwer J ((2006) TGN1412 — a regulator’s perspective. Nat Biotechnol 24(5):493–496
Suntharalingam G, Perry MR, Ward S, Brett SJ, Castello-Cortes A, Brunner MD, Panoskaltsis N (2006) Cytokine storm in a phase 1 trial of the anti-CD28 monoclonal antibody TGN1412. N Engl J Med Sep 7; 355(10):1018–1028
Taylor PC (2007) Biologic therapies for rheumatoid arthritis targeting TNF-α and IL-1. In: Boehncke W-H, Radeke HH (eds) Biologics in general medicine, Chapter 11. Springer-Verlag, Heidelberg [this volume]
Van Assche G, Van Ranst M, Sciot R, Dubois B, Vermeire S, Noman M, Verbeeck J, Geboes K, Robberecht W, Rutgeerts P (2005) Progressive multifocal leukoencephalopathy after natalizumab therapy for Crohn’s disease. N Engl J Med 353(4):362–368
Vlachaki E, Psathakis K, Tsintiris K, Iliopoulos A (2005) Delayed response to anti-tuberculosis treatment in a patient on infliximab. Respir Med 99(5):648–652
Wallis RS, Ehlers S (2005) Tumor necrosis factor and granuloma biology: explaining the differential infection risk of etanercept and infliximab. Semin Arthritis Rheum 34(5 Suppl 1):34–38
Yarden Y, Sliwkowski MX (2001) Untangling the ErbB signaling network. Nat RevMol Cell Biol 2:127–137
Yednock TA, Cannon C, Fritz LC, Sanchez-Madrid F, Steinman L, Karin N (1992) Prevention of experimental autoimmune encephalomyelitis by antibodies against alpha 4 beta 1 integrin. Nature 356(6364):63–66
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2007 Springer-Verlag Berlin Heidelberg
About this chapter
Cite this chapter
Schneider, C.K., Löwer, J. (2007). Safety Aspects of Biologics: Lessons Learnt from Monoclonal Antibodies. In: Boehncke, WH., Radeke, H.H. (eds) Biologics in General Medicine. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-29018-6_16
Download citation
DOI: https://doi.org/10.1007/978-3-540-29018-6_16
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-540-29017-9
Online ISBN: 978-3-540-29018-6
eBook Packages: MedicineMedicine (R0)