Monoklonale Antikörper

 

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Zusammenfassung

Steigende Zulassungsraten für Monoklonale Antikörper (MAK) zur Therapie von Krebs, Autoimmun- und zuletzt auch kardiovaskulären Erkrankungen zeigen die wachsende Bedeutung dieser seit Ende des 19. Jahrhunderts bekannten, aber erst seit den 1980er kommerzialisierten und klinisch kontrollierten Therapieoption. Der vorliegende Beitrag fasst die historische Entwicklung der monoklonalen Antikörpertherapie, den status-quo der klinischen Zulassung, sowie die zukünftigen Perspektiven durch neuartige MAKs und deren Derivaten zusammen.

Abstract

Rising numbers of approved monoclonal antibodies for cancer, autoimmune and cardiovascular disease treatment underline the growing importance of this therapeutic option which has been discovered in the late 19th century. However, clinical trials and commercial use started in the late 20th century. The specific mode of action and clinical advantages over standard strategies signify a big step forward not only in terms of treating cancer but various other diseases like psoriasis and multiple sclerosis. New developments in the field of biologicals raise hope for an even broader scope of applications and options for currently untreatable diseases. The following article summarizes the historical development, the status-quo of clinical approvement and current development of monoclonal antibody therapy.

• Literatur

• 1 Murphy JR. Corynebacterium Diphtheriae. In: Baron S, Hrsg. Medical Microbiology. 4th. Aufl. Galveston (TX): 1996
  Google Scholar
• 2 Ribatti D. Edelman’s view on the discovery of antibodies. Immunol Lett 2015; 164: 72-75
  CrossrefPubMedGoogle Scholar
• 3 Padlan EA. Anatomy of the antibody molecule. Mol Immunol 1994; 31: 169-217
  CrossrefPubMedGoogle Scholar
• 4 Kapur R, Einarsdottir HK, Vidarsson G. IgG-effector functions: “the good, the bad and the ugly”. Immunol Lett 2014; 160: 139-144
  CrossrefPubMedGoogle Scholar
• 5 Sgro C. Side-effects of a monoclonal antibody, muromonab CD3/orthoclone OKT3: bibliographic review. Toxicology 1995; 105: 23-29
  CrossrefPubMedGoogle Scholar
• 6 Foltz IN, Karow M, Wasserman SM. Evolution and emergence of therapeutic monoclonal antibodies: what cardiologists need to know. Circulation 2013; 127: 2222-2230
  CrossrefPubMedGoogle Scholar
• 7 Liu JK. The history of monoclonal antibody development - Progress, remaining challenges and future innovations. Ann Med Surg 2014; 3: 113-116
  PubMedGoogle Scholar
• 8 Ferrara N, Hillan KJ, Novotny W. Bevacizumab (Avastin), a humanized anti-VEGF monoclonal antibody for cancer therapy. Biochemical and biophysical research communications 2005; 333: 328-335
  CrossrefPubMedGoogle Scholar
• 9 Yamada T. Therapeutic monoclonal antibodies. Keio J Med 2011; 60: 37-46
  CrossrefPubMedGoogle Scholar
• 10 Tabrizi MA, Tseng CM, Roskos LK. Elimination mechanisms of therapeutic monoclonal antibodies. Drug Discov Today 2006; 11: 81-88
  CrossrefPubMedGoogle Scholar
• 11 Dige A, Hvas CL, Deleuran B et al. Adalimumab treatment in Crohn’s disease does not induce early changes in regulatory T cells. Scand J Gastroenterol 2011; 46: 1206-1214
  CrossrefPubMedGoogle Scholar
• 12 Hansel TT, Kropshofer H, Singer T et al. The safety and side effects of monoclonal antibodies. Nat Rev Drug Discov 2010; 9: 325-338
  CrossrefPubMedGoogle Scholar
• 13 Vultaggio A, Maggi E, Matucci A. Immediate adverse reactions to biologicals: from pathogenic mechanisms to prophylactic management. Curr Opin Allergy Clin Immunol 2011; 11: 262-268
  CrossrefPubMedGoogle Scholar
• 14 Smith I, Procter M, Gelber RD et al. 2-year follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer: a randomised controlled trial. Lancet 2007; 369: 29-36
  CrossrefPubMedGoogle Scholar
• 15 Suntharalingam G, Perry MR, Ward S et al. Cytokine storm in a phase 1 trial of the anti-CD28 monoclonal antibody TGN1412. N Engl J Med 2006; 355: 1018-1028
  CrossrefPubMedGoogle Scholar
• 16 Ecker DM, Jones SD, Levine HL. The therapeutic monoclonal antibody market. mAbs 2015; 7: 9-14
  CrossrefPubMedGoogle Scholar
• 17 Bang YJ, Van Cutsem E, Feyereislova A et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet 2010; 376: 687-697
  CrossrefPubMedGoogle Scholar
• 18 Hurwitz H, Fehrenbacher L, Novotny W et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. The New England journal of medicine 2004; 350: 2335-2342
  CrossrefPubMedGoogle Scholar
• 19 Perez-Gala S, Delgado-Jimenez Y, Goiriz R et al. Cytokine-release syndrome related to rituximab limited to lesions and excision scars of lesions of primary cutaneous lymphoma. Arch Dermatol 2006; 142: 1516-1517
  PubMedGoogle Scholar
• 20 Hamid O, Robert C, Daud A et al. Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma. N Engl J Med 2013; 369: 134-144
  CrossrefPubMedGoogle Scholar
• 21 Fleischmann RM, Halland AM, Brzosko M et al. Tocilizumab inhibits structural joint damage and improves physical function in patients with rheumatoid arthritis and inadequate responses to methotrexate: LITHE study 2-year results. J Rheumatol 2013; 40: 113-126
  CrossrefPubMedGoogle Scholar
• 22 Grasland A, Mahe E, Raynaud E et al. Psoriasis onset with tocilizumab. Joint Bone Spine 2013; 80: 541-542
  CrossrefPubMedGoogle Scholar
• 23 Singh JA, Christensen R, Wells GA et al. Biologics for rheumatoid arthritis: an overview of Cochrane reviews. Cochrane Database Syst Rev 2009; DOI: 10.1002/14651858.CD007848.pub2: CD007848.
  PubMedGoogle Scholar
• 24 van der Heijde D, Breban M, Halter D et al. Maintenance of improvement in spinal mobility, physical function and quality of life in patients with ankylosing spondylitis after 5 years in a clinical trial of adalimumab. Rheumatology 2015; 54: 1210-1219
  CrossrefPubMedGoogle Scholar
• 25 Bridel C, Lalive PH. Update on multiple sclerosis treatments. Swiss Med Wkly 2014; 144: w14012
  PubMedGoogle Scholar
• 26 King S, Short M, Harmon C. Glycoprotein IIb/IIIa inhibitors: The resurgence of tirofiban. Vasc Pharmacol 2015; DOI: 10.1016/j.vph.2015.07.008.
  PubMedGoogle Scholar
• 27 Garber K. Bispecific antibodies rise again. Nat Rev Drug Discov 2014; 13: 799-801
  CrossrefPubMedGoogle Scholar
• 28 Topp MS, Kufer P, Gokbuget N et al. Targeted therapy with the T-cell-engaging antibody blinatumomab of chemotherapy-refractory minimal residual disease in B-lineage acute lymphoblastic leukemia patients results in high response rate and prolonged leukemia-free survival. J Clin Oncol 2011; 29: 2493-2498
  CrossrefPubMedGoogle Scholar
• 29 Zugmaier G, Gokbuget N, Klinger M et al. Long-term survival and T-Cell kinetics in adult patients with relapsed/refractory B-precursor acute lymphoblastic leukemia who achieved minimal residual disease response following treatment with Anti-CD19 BiTE(R) antibody construct blinatumomab. Blood 2015; DOI: 10.1182/blood-2015-06-649111.
  PubMedGoogle Scholar
• 30 Chari RV, Miller ML, Widdison WC. Antibody-drug conjugates: an emerging concept in cancer therapy. Angewandte Chemie 2014; 53: 3796-3827
  CrossrefPubMedGoogle Scholar
• 31 Zolot RS, Basu S, Million RP. Antibody-drug conjugates. Nat Rev Drug Discov 2013; 12: 259-260
  CrossrefPubMedGoogle Scholar
• 32 Hoelzer D. Targeted therapy with monoclonal antibodies in acute lymphoblastic leukemia. Curr Opin Oncol 2013; 25: 701-706
  CrossrefPubMedGoogle Scholar