Monoklonale Antikörper

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.

Schlüsselwörter

Monoklonale Antikörper - Immunmodulation - Biologicals - bi-spezifische Antikörper - Antibody-Drug Conjugates

• Literatur

• 1 Murphy JR. Corynebacterium Diphtheriae. In: Baron S, Hrsg. Medical Microbiology. 4th. Aufl. Galveston (TX): 1996
• 2 Ribatti D. Edelman’s view on the discovery of antibodies. Immunol Lett 2015; 164: 72-75
• 3 Padlan EA. Anatomy of the antibody molecule. Mol Immunol 1994; 31: 169-217
• 4 Kapur R, Einarsdottir HK, Vidarsson G. IgG-effector functions: “the good, the bad and the ugly”. Immunol Lett 2014; 160: 139-144
• 5 Sgro C. Side-effects of a monoclonal antibody, muromonab CD3/orthoclone OKT3: bibliographic review. Toxicology 1995; 105: 23-29
• 6 Foltz IN, Karow M, Wasserman SM. Evolution and emergence of therapeutic monoclonal antibodies: what cardiologists need to know. Circulation 2013; 127: 2222-2230
• 7 Liu JK. The history of monoclonal antibody development - Progress, remaining challenges and future innovations. Ann Med Surg 2014; 3: 113-116
• 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
• 9 Yamada T. Therapeutic monoclonal antibodies. Keio J Med 2011; 60: 37-46
• 10 Tabrizi MA, Tseng CM, Roskos LK. Elimination mechanisms of therapeutic monoclonal antibodies. Drug Discov Today 2006; 11: 81-88
• 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
• 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
• 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
• 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
• 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
• 16 Ecker DM, Jones SD, Levine HL. The therapeutic monoclonal antibody market. mAbs 2015; 7: 9-14
• 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
• 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
• 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
• 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
• 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
• 22 Grasland A, Mahe E, Raynaud E et al. Psoriasis onset with tocilizumab. Joint Bone Spine 2013; 80: 541-542
• 23 Singh JA, Christensen R, Wells GA et al. Biologics for rheumatoid arthritis: an overview of Cochrane reviews. Cochrane Database Syst Rev 2009;
• 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
• 25 Bridel C, Lalive PH. Update on multiple sclerosis treatments. Swiss Med Wkly 2014; 144: w14012
• 26 King S, Short M, Harmon C. Glycoprotein IIb/IIIa inhibitors: The resurgence of tirofiban. Vasc Pharmacol 2015;
• 27 Garber K. Bispecific antibodies rise again. Nat Rev Drug Discov 2014; 13: 799-801
• 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
• 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;
• 30 Chari RV, Miller ML, Widdison WC. Antibody-drug conjugates: an emerging concept in cancer therapy. Angewandte Chemie 2014; 53: 3796-3827
• 31 Zolot RS, Basu S, Million RP. Antibody-drug conjugates. Nat Rev Drug Discov 2013; 12: 259-260
• 32 Hoelzer D. Targeted therapy with monoclonal antibodies in acute lymphoblastic leukemia. Curr Opin Oncol 2013; 25: 701-706