B-cell-targeted treatment for multiple sclerosis: Mechanism of action and clinical data

Current Opinion in Neurology

Volumn 21, Issue SUPPL. 1, 2008, Pages

  Hawker, Kathleen ^a  

^a OHIO STATE UNIVERSITY   (United States)

Author keywords

Autoimmune; B cell targeted; Depletion; Epratuzumab; Multiple sclerosis; Rituximab

Indexed keywords

ABATACEPT; ABETIMUS; ATACICEPT; BELIMUMAB; BETA INTERFERON; CYCLOPHOSPHAMIDE; DC 2219; DIPHTHERIA TOXIN; EPRATUZUMAB; GLATIRAMER; IMMU 103; IMMUNOGLOBULIN; IMMUNOTOXIN; MITOXANTRONE; NATALIZUMAB; PLACEBO; RITUXIMAB; SINGLE CHAIN FRAGMENT VARIABLE ANTIBODY; UNCLASSIFIED DRUG;

B LYMPHOCYTE; CLINICAL STUDY; CLINICAL TRIAL; DISEASE COURSE; DRUG MECHANISM; FOOD AND DRUG ADMINISTRATION; HUMAN; MULTIPLE SCLEROSIS; NONHUMAN; REVIEW; UNSPECIFIED SIDE EFFECT;

ANIMALS; ANTIBODIES, MONOCLONAL; B-LYMPHOCYTES; HUMANS; IMMUNOLOGIC FACTORS; MULTIPLE SCLEROSIS; OLIGONUCLEOTIDES; RECOMBINANT FUSION PROTEINS;

EID: 41649114547     PISSN: 13507540     EISSN: None     Source Type: Journal    
DOI: 10.1097/01.wco.0000313360.38306.ab     Document Type: Review

References (74)

1. Martin F, Chan AC. Pathogenic roles of B cells in human autoimmunity; insights from the clinic. Immunity 2004; 20:517-527.
2. Dalakas MC. B cells in the pathophysiology of autoimmune neurological disorders: a credible therapeutic target. Pharmacol Ther 2006; 112:57-70.
3. Racke M. The role of B cells in multiple sclerosis: rationale for B-cell-targeted therapies. Curr Opin Neurol 2008; 21 (Suppl. 1):S9-S18.
4. Hahn AF. Guillain-Barre syndrome. Lancet 1998; 352:635-641.
5. Cross AH, Trotter JL, Lyons J. B cells and antibodies in CNS demyelinating disease. J Neuroimmunol 2001; 112:1-14.
6. Wucherpfennig KW, Catz I, Hausmann S, et al. Recognition of the immunodominant myelin basic protein peptide by autoantibodies and HLA-DR2-restricted T cell clones from multiple sclerosis patients. Identity of key contact residues in the B-cell and T-cell epitopes. J Clin Invest 1997; 100:1114-1122.
7. Cannella B, Raine CS. The adhesion molecule and cytokine profile of multiple sclerosis lesions. Ann Neurol 1995; 37:424-435.
8. Knopf PM, Harling-Berg CJ, Cserr HF, et al. Antigen-dependent intrathecal antibody synthesis in the normal rat brain: tissue entry and local retention of antigen-specific B cells. J Immunol 1998; 161:692-701.
9. Corcione A, Casazza S, Ferretti E, et al. Recapitulation of B cell differentiation in the central nervous system of patients with multiple sclerosis. Proc Natl Acad Sci U S A 2004; 101:11064-11069.
10. Meinl E, Krumbholz M, Hohlfeld R. B lineage cells in the inflammatory central nervous system environment: migration, maintenance, local antibody production, and therapeutic modulation. Ann Neurol 2006; 59:880-892.
11. Qin Y, Duquette P, Zhang Y, et al. Intrathecal B-cell clonal expansion, an early sign of humoral immunity, in the cerebrospinal fluid of patients with clinically isolated syndrome suggestive of multiple sclerosis. Lab Invest 2003; 83:1081-1088.
12. Villar LM, Masjuan J, Gonzalez-Porque P, et al. Intrathecal IgM synthesis in neurologic diseases: relationship with disability in MS. Neurology 2002; 58:824-826.
13. Esiri MM. Immunoglobulin-containing cells in multiple-sclerosis plaques. Lancet 1977; 2:478.
14. Serafini B, Rosicarelli B, Magliozzi R, et al. Detection of ectopic B-cell follicles with germinal centers in the meninges of patients with secondary progressive multiple sclerosis. Brain Pathol 2004; 14:164-174.
15. Lyons JA, Ramsbottom MJ, Cross AH. Critical role of antigen-specific antibody in experimental autoimmune encephalomyelitis induced by recombinant myelin oligodendrocyte glycoprotein. Eur J Immunol 2002; 32:1905-1913.
16. Mesleh MF, Belmar N, Lu CW, et al. Marmoset fine B cell and T cell epitope specificities mapped onto a homology model of the extracellular domain of human myelin oligodendrocyte glycoprotein. Neurobiol Dis 2002; 9:160-172.
17. Gay FW, Drye TJ, Dick GW, Esiri MM. The application of multifactorial cluster analysis in the staging of plaques in early multiple sclerosis. Identification and characterization of the primary demyelinating lesion. Brain 1997; 120:1461-1483.
18. Lucchinetti C, Bruck W, Parisi J, et al. Heterogeneity of multiple sclerosis lesions: implications for the pathogenesis of demyelination. Ann Neurol 2000; 47:707-717.
19. Chofflon M. Mechanisms of action for treatments in multiple sclerosis: does a heterogeneous disease demand a multi-targeted therapeutic approach? BioDrugs 2005; 19:299-308.
20. Chan A, Weilbach FX, Toyka KV, Gold R. Mitoxantrone induces cell death in peripheral blood leucocytes of multiple sclerosis patients. Clin Exp Immunol 2005; 139:152-158.
21. Novantrone (package insert). Melville, NY: OSI Pharmaceuticals Inc.; 2007.
22. Cree B. Emerging monoclonal antibody therapies for multiple sclerosis. Neurologist 2006; 12:171-178.
23. Edwards JC, Cambridge G. B-cell targeting in rheumatoid arthritis and other autoimmune diseases. Nat Rev Immunol 2006; 6:394-403.
24. Rituxan (package insert). South San Francisco, CA: Genentech, Inc.; 2006.
25. Carnahan J, Stein R, Qu Z, et al. Epratuzumab, a CD22-targeting recombinant humanized antibody with a different mode of action from rituximab. Mol Immunol 2007; 44:1331-1341.
26. Carnahan J, Wang P, Kendall R, et al. Epratuzumab, a humanized monoclonal antibody targeting CD22: characterization of in vitro properties. Clin Cancer Res 2003; 9:3982S-3990S.
27. Anolik JH, Aringer M. New treatments for SLE: cell-depleting and anti-cytokine therapies. Best Pract Res Clin Rheumatol 2005; 19:859-878.
28. Bristol-Myers Squibb, 345 Park Avenue, New York, New York 10154. A phase II, randomized,double-blind, placebo controlled study to evaluate the preliminary efficacy, pharmacokinetics and immunogenicity of BMS-188667 administered to subjects with relapsing-remitting multiple sclerosis. Clinical Study Report IM101200. Bristol-Myers Squibb; 2004.
29. Hartung HP, Bar-Or A, Zoukos Y. What do we know about the mechanism of action of disease-modifying treatments in MS? J Neurol 2004; 251 (Suppl. 5): v12-v29.
30. Grillo-Lopez AJ, Hedrick E, Rashford M, Benyunes M. Rituximab: ongoing and future clinical development. Semin Oncol 2002; 29:105-112.
31. Pijpe J, van Imhoff GW, Spijkervet FK, et al. Rituximab treatment in patients with primary Sjogren's syndrome: an open-label phase II study. Arthritis Rheum 2005; 52:2740-2750.
32. Tokunaga M, Saito K, Kawabata D, et al. Efficacy of rituximab (Anti-CD20) for refractory systemic lupus erythematosus involving the central nervous system. Ann Rheum Dis 2007; 66:470-475.
33. Kotani T, Takeuchi T, Kawasaki Y, et al. Successful treatment of cold agglutinin disease with anti-CD20 antibody (rituximab) in a patient with systemic lupus erythematosus. Lupus 2006; 15:683-685.
34. Hauser S. A phase II randomized, placebo-controlled, multicenter trial of rituximab in adults with relapsing remitting multiple sclerosis (RRMS). In: 59th Annual Meeting of the American Academy of Neurology. Boston, MA, 1 May 2007 [Abstract S12.003].
35. Waubant E. Safety and efficacy of rituximab in adults with relapsing-remitting multiple sclerosis: results of a phase II placebo-controlled, multicentre trial through 48 weeks. In: ECTRIMS 2007. Prague, Czech Republic, 13 October 2007 [Abstract P554].
36. Monson NL, Cravens PD, Frohman EM, et al. Effect of rituximab on the peripheral blood and cerebrospinal fluid B cells in patients with primary progressive multiple sclerosis. Arch Neurol 2005; 62:258-264.
37. Stuve O, Cepok S, Elias B, et al. Clinical stabilization and effective B-lymphocyte depletion in the cerebrospinal fluid and peripheral blood of a patient with fulminant relapsing-remitting multiple sclerosis. Arch Neurol 2005; 62:1620-1623.
38. Petereit HF, Rubbert A. Effective suppression of cerebrospinal fluid B cells by rituximab and cyclophosphamide in progressive multiple sclerosis. Arch Neurol 2005; 62:1641-1642.
39. Cross AH, Stark JL, Lauber J, et al. Rituximab reduces B cells and T cells in cerebrospinal fluid of multiple sclerosis patients. J Neuroimmunol 2006; 180:63-70.
40. Genentech. Genentech and Biogen Idec announce positive results from a phase II trial of Rituxan in relapsing-remitting multiple sclerosis. 28 August 2006. Internet 2007 (cited 31 January 2007) Available at: http://www.gene.com/ gene/news/press-releases/display.do?method=detail&id=9987, Accessed January 31, 2007.
41. Cesano A, Gayko U. CD22 as a target of passive immunotherapy. Semin Oncol 2003; 30:253-257.
42. Dorner T, Kaufmann J, Wegener WA, et al. Initial clinical trial of epratuzumab (humanized anti-CD22 antibody) for immunotherapy of systemic lupus erythematosus. Arthritis Res Ther 2006; 8:R74.
43. Steinfeld SD, Tant L, Burmester GR, et al. Epratuzumab (humanised anti-CD22 antibody) in primary Sjogren's syndrome: an open-label phase I/II study. Arthritis Res Ther 2006; 8:R129.
44. Strauss SJ, Morschhauser F, Rech J, et al. Multicenter phase II trial of immunotherapy with the humanized anti-CD22 antibody, epratuzumab, in combination with rituximab, in refractory or recurrent non-Hodgkin's lymphoma. J Clin Oncol 2006; 24:3880-3886.
45. Vallera DA, Todhunter DA, Kuroki DW, et al. A bispecific recombinant immunotoxin, DT2219, targeting human CD19 and CD22 receptors in a mouse xenograft model of B-cell leukemia/lymphoma. Clin Cancer Res 2005; 11:3879-3888.
46. MacKay F, Sierro F, Grey ST, Gordon TP. The BAFF/APRIL system: an important player in systemic rheumatic diseases. Curr Dir Autoimmun 2005; 8:243-265.
47. Krumbholz M, Theil D, Derfuss T, et al. BAFF is produced by astrocytes and up-regulated in multiple sclerosis lesions and primary central nervous system lymphoma. J Exp Med 2005; 201:195-200.
48. Furie R, Lisse J, Merrill JT, et al. Belimumab (fully human monoclonal antibody to B-lymphocyte stimulator [BLyS]) improves or stabilizes SLE activity in a multicenter phase 2 trial. In: 70th Annual Meeting of the American College of Rheumatology. Washington, DC, 11-15 November 2006 [Abstract 535].
49. Wallace DJ. Belimumab (BmAb) reduces SLE disease activity and demonstrates durable bioactivity at 76 weeks. In: 70th Annual Meeting of the American College of Rheumatology. Washington, DC, 11-15 November 2006 [Abstract 2012].
50. Parrott J. Human Genome Sciences announces positive 76-week results of phase 2 clinical trial of LymphoStat-B in systemic lupus erythematosus. Human Genome Sciences Press Release, 14 November 2006.
51. McKay J. Belimumab (BmAb), a fully human monoclonal antibody to B-lymphocyte stimulator (BLyS), combined with standard of care therapy reduces the signs and symptoms of rheumatoid arthritis in a heterogenous subject population. In: 69th Annual Meeting of the American College of Rheumatology. San Diego, CA, 12-17 November 2005 [Abstract 1920].
52. Zhang X, Park CS, Yoon SO, et al. BAFF supports human B cell differentiation in the lymphoid follicles through distinct receptors. Int Immunol 2005; 17:779-788.
53. Zheng Y, Gallucci S, Gaughan JP, et al. A role for B cell-activating factor of the TNF family in chemically induced autoimmunity. J Immunol 2005; 175:6163-6168.
54. Gross JA, Dillon SR, Mudri S, et al. TACI-Ig neutralizes molecules critical for B cell development and autoimmune disease. impaired B cell maturation in mice lacking BLyS. Immunity 2001; 15:289-302.
55. Ramanujam M, Wang X, Huang W, et al. Mechanism of action of transmembrane activator and calcium modulator ligand interactor-Ig in murine systemic lupus erythematosus. J Immunol 2004; 173:3524-3534.
56. ZymoGenetics. ZymoGenetics highlights development programs at annual analyst & investor briefing. ZymoGenetics News Release, 14 December 2006.
57. Dall'Era M. Trial of atacicept in patients with systemic lupus erythematosus (SLE). In: 70th Annual Meeting of the American College of Rheumatology. Washington, DC, 11-15 November 2006 [Abstract L19/499].
58. ZymoGenetics. ZymoGenetics releases preliminary findings from atacicept (TACI-Ig) phase 1b studies in patients with lupus. ZymoGenetics News Release, 25 July 2006.
59. Tak PP. A phase Ib study to investigate atacicept (TACI-Ig) in patients with rheumatoid arthritis. In: 70th Annual Meeting of the American College of Rheumatology. Washington, DC, 11-15 November 2006 [Abstract L36/516].
60. ZymoGenetics. ZymoGenetics and Serono begin phase 2 clinical trial with atacicept in rheumatoid arthritis. ZymoGenetics News Release, 20 December 2006.
61. Ansell S. Phase I clinical study of atacicept in patients with relapsed and refractory B-cell lymphoma. Blood 2006; 108 (Suppl):A2722.
62. Rossi JF. A phase I/II study of atacicept (TACI-Ig) to neutralize APRIL and BLyS in patients with refractory or relapsed multiple myeloma (MM) or active previously treated Waldenstrom's macroglobulinemia (WM). Blood 2006; 108 (Suppl):A3578.
63. Kremer JM, Genant HK, Moreland LW, et al. Effects of abatacept in patients with methotrexate-resistant active rheumatoid arthritis: a randomized trial. Ann Intern Med 2006; 144:865-876.
64. Mena E, Rohowsky-Kochan C. Expression of costimulatory molecules on peripheral blood mononuclear cells in multiple sclerosis. Acta Neurol Scand 1999; 100:92-96.
65. Reynolds J, Tam FW, Chandraker A, et al. CD28-B7 blockade prevents the development of experimental autoimmune glomerulonephritis. J Clin Invest 2000; 105:643-651.
66. Kremer JM. Selective costimulation modulators: a novel approach for the treatment of rheumatoid arthritis. J Clin Rheumatol 2005; 11 (Suppl. 3):S55-S62.
67. Abe S, Hanawa H, Hayashi M, et al. Prevention of experimental autoimmune myocarditis by hydrodynamics-based naked plasmid DNA encoding CTLA4-Ig gene delivery. J Cardiac Fail 2005; 11:557-564.
68. Alegre ML, Fallarino F. Mechanisms of CTLA-4-Ig in tolerance induction. Curr Pharm Des 2006; 12:149-160.
69. Lovett-Racke AE, Trotter JL, Lauber J, et al. Decreased dependence of myelin basic protein-reactive T cells on CD28-mediated costimulation in multiple sclerosis patients. A marker of activated/memory T cells. J Clin Invest 1998; 101:725-730.
70. Orencia (package insert). Princeton, NJ: Bristol-Myers Squibb Company; January 2007.
71. Hervey PS, Keam SJ. Abatacept. BioDrugs 2006; 20:53-61.
72. Weinblatt M, Combe B, Covucci A, et al. Safety of the selective costimulation modulator abatacept in rheumatoid arthritis patients receiving background biologic and nonbiologic disease-modifying antirheumatic drugs: a one-year randomized, placebo-controlled study. Arthritis Rheum 2006; 54:2807-2816.
73. Alarcon-Segovia D, Tumlin JA, Furie RA, et al. LJP 394 for the prevention of renal flare in patients with systemic lupus erythematosus: results from a randomized, double-blind, placebo-controlled study. Arthritis Rheum 2003; 48:442-454.
74. Linnik MD. Progressive reduction in risk of renal flare in SLE patients is associated with improved long-term control of anti-dsDNA antibody levels. In: 69th Annual Meeting of the American College of Rheumatology. San Diego, CA, 12-17 November 2005 [Abstract 441].