Complement-targeted therapy: development of C5- and C5a-targeted inhibition
Tóm tắt
The complement system is a major effector of humoral immunity and natural immunity. The complement system has three independent pathways of complement activation: a classical pathway, an alternative pathway, and a lectin pathway. These pathways converge to a common pathway that activates C3. This pathway also leads to the formation of various bioactive molecules such as C5a and the formation of membrane attack complex on the surface of target cells. In the past, the only preparations with anti-complementary action were C1 inhibitors (C1-INH), but an anti-C5 monoclonal antibody (eculizumab) appeared a few years ago, and this antibody has yielded encouraging results. In addition, a C5a receptor (C5aR) antagonist is in the clinical trial phase, and this antagonist should also prove efficacious. Anti-complement agents have garnered attention as a new treatment strategy for refractory inflammatory diseases.
Tài liệu tham khảo
Ricklin D, Lambris JD. Complement in immune and inflammatory disorders: pathophysiological mechanisms. J Immunol. 2013;190:3831–8.
Tsukamoto H, Horiuchi T. Clinical aspects of the complement system. Rinsho Byori. 2006;54:757–62.
Hillmen P, Young NS, Schubert J, et al. The complement inhibitor eculizumab in paroxysmal nocturnal hemoglobinuria. N Engl J Med. 2006;355:1233–43.
Gruppo RA, Rother RP. Eculizumab for congenital atypical hemolytic-uremic syndrome. N Engl J Med. 2009;360:544–6.
Matis LA, Rollins SA. Complement-specific antibodies: designing novel anti-inflammatories. Nat Med. 1995;1:839–42.
Jayne DR, Bruchfeld A, Schaier M, et al. Oral C5a receptor antagonist CCX168 phase II clinical trial in ANCA-associated renal vasculitis. Ann Rheum Dis. 2014;73 Suppl 2:148. abstract.
Bekker P, Jayne D, Bruchfeld A, et al. CCX168, an orally administered C5aR inhibitor for treatment of patients with antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheumatol. 2014;66:S820. abstract.
Horiuchi T, Mitoma H, Harashima S-I, et al. Transmembrane TNF-alpha: structure, function and interaction with anti-TNF agents. Rheumatology (Oxford). 2010;49:1215–28.
Mitoma H, Horiuchi T, Tsukamoto H, et al. Mechanisms for cytotoxic effects of anti-tumor necrosis factor agents on transmembrane tumor necrosis factor alpha-expressing cells. Arthritis Rheum. 2008;58:1248–57.
Horiuchi T, Ohi H, Ohsawa I, et al. Guideline for hereditary angioedema (HAE) 2010 by the Japanese Association for Complement Research—secondary publication. Allergol Int. 2012;61:559–62.
Reis ES, Mastellos DC, Yancopoulou D, et al. Applying complement therapeutics to rare diseases. Clin Immunol. 2015;161:225–40.
Brodsky RA. Complement in hemolytic anemia. Blood. 2015;126:2459–65.
Kaplan BS, Ruebner RL, Spinale JM, et al. Current treatment of atypical hemolytic uremic syndrome. Intractable Rare Dis Res. 2014;3:34–45.
Noris M, Mescia F, Remuzzi G. STEC-HUS, atypical HUS and TTP are all diseases of complement activation. Nat Rev Nephrol. 2012;8:622–33.
Woodruff TM, Nandakumar KS, Tedesco F. Inhibiting the C5-C5a receptor axis. Mol Immunol. 2011;48:1631–42.
Jose PJ, Moss IK, Maini RN, et al. Measurement of the chemotactic complement fragment C5a in rheumatoid synovial fluids by radioimmunoassay: role of C5a in the acute inflammatory phase. Ann Rheum Dis. 1990;49:747–52.
Plenge RM, Seielstad M, Padyukov L, et al. TRAF1-C5 as a risk locus for rheumatoid arthritis—a genomewide study. N Engl J Med. 2007;357:1199–209.
Nishimoto K, Kochi Y, Ikari K, et al. Association study of TRAF1-C5 polymorphism with susceptibility to rheumatoid arthritis and systemic lupus erythematosus in Japanese. Ann Rheum Dis. 2010;69:368–73.
Johansson AC, Sundler M, Kjellen P, et al. Genetic control of collagen-induced arthritis in a cross with NOD and C57BL/10 mice is dependent on gene regions encoding complement factor 5 and FcgammaRIIb and is not associated with loci controlling diabetes. Eur J Immunol. 2001;31:1847–56.
Lindqvis AK, Johannesson M, Johansson AC, et al. Backcross and partial advanced intercross analysis of nonobese diabetic gene-mediated effects on collagen-induced arthritis reveals an interactive effect by two major loci. J Immunol. 2006;177:3952–9.
Wang Y, Kristan J, Hao L, et al. A role for complement in antibody-mediated inflammation: C5-deficient DBA/1 mice are resistant to collagen-induced arthritis. J Immunol. 2000;164:4340–7.
Ji H, Gauquier D, Ohmura K, et al. Genetic influences on the end-stage effector phase of arthritis. J Exp Med. 2001;194:321–30.
Vergunst CE, Gerlag DM, Dinant H, et al. Blocking the receptor for C5a in patients with rheumatoid arthritis does not reduce synovial inflammation. Rheumatology (Oxford). 2007;46:1773–8.
Mojcik CF, Kremer J, Bingham C, et al. Results of a phase 2b study of the humanized anti-C5 antibody eculizumab in patients with rheumatoid arthritis. Ann Rheum Dis. 2004;63 Suppl 1:301. abstract.
Yuan J, Gou SJ, Huang J, et al. C5a and its receptors in human anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Arthritis Res Ther. 2012;14:R140.
Gou S-J, Yuan J, Chen M, et al. Circulating complement activation in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis. Kidney Int. 2012;83:129–37.
Xiao H, Schreiber A, Heeringa P, et al. Alternative complement pathway in the pathogenesis of disease mediated by anti-neutrophil cytoplasmic autoantibodies. Am J Pathol. 2007;170:52–64.
Huugen D, van Esch A, Xiao H, et al. Inhibition of complement factor C5 protects against anti-myeloperoxidase antibody-mediated glomerulonephritis in mice. Kidney Int. 2007;71:646–54.
Xiao H, Dairaghi DJ, Powers JP, et al. C5a receptor (CD88) blockade protects against MPO-ANCA GN. J Am Soc Nephrol. 2014;25:225–31.
Klos A, Tenner AJ, Johswich K-O, et al. The role of the anaphylatoxins in health and disease. Mol Immunol. 2009;46:2753–66.
Ricklin D, Lambris JD. Complement in immune and inflammatory disorders: therapeutic interventions. J Immunol. 2013;190:3839–47.