Novel targeted therapies for autoimmunity

Current Opinion in Immunology

Volumn 21, Issue 6, 2009, Pages 648-657

  St Clair, E William ^a  

^a DUKE UNIVERSITY MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ABATACEPT; ALEFACEPT; ALEMTUZUMAB; BETA1A INTERFERON; BHT 3021; CD3 ANTIBODY; CORTICOSTEROID; CYTOKINE ANTIBODY; DACLIZUMAB; DIRUCOTIDE; FC RECEPTOR; GLATIRAMER; GLUTAMATE DECARBOXYLASE; GLUTAMATE DEHYDROGENASE; INTERLEUKIN 12 ANTIBODY; INTERLEUKIN 23; INTERLEUKIN 6 RECEPTOR; OTELIXIZUMAB; PEPTIDE; PEPTIDE VACCINE; PLACEBO; PROINSULIN; PROTEIN KINASE INHIBITOR; RAPAMYCIN; RECEPTOR ANTIBODY; RITUXIMAB; SPHINGOSINE 1 PHOSPHATE; TEPILIZUMAB; UNCLASSIFIED DRUG; UNINDEXED DRUG; VISILIZUMAB;

AUTOIMMUNE DISEASE; AUTOIMMUNE THYROIDITIS; AUTOIMMUNITY; B LYMPHOCYTE; CLINICAL TRIAL; DRUG INDICATION; DRUG TARGETING; HUMAN; IMMUNE RESPONSE; IMMUNOLOGICAL TOLERANCE; IMMUNOREGULATION; INFLAMMATION; INSULIN DEPENDENT DIABETES MELLITUS; LUPUS ERYTHEMATOSUS NEPHRITIS; LUPUS VULGARIS; MULTIPLE SCLEROSIS; PEMPHIGUS VULGARIS; PSORIASIS; REVIEW; RHEUMATOID ARTHRITIS; T LYMPHOCYTE; THROMBOCYTOPENIC PURPURA; ULCERATIVE COLITIS;

ANIMALS; AUTOIMMUNE DISEASES; CYTOKINES; HUMANS; IMMUNE TOLERANCE; LYMPHOCYTES; RECEPTORS, IMMUNOLOGIC;

EID: 70449495408     PISSN: 09527915     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.coi.2009.09.008     Document Type: Review

References (69)

1. Ruderman E.M., and Pope R.M. Drug insight: abatacept for the treatment of rheumatoid arthritis. Nat Clin Pract Rheumatol 12 (2006) 654-660
2. Vincenti F., and Luggen M. T cell costimulation: a rational target in the therapeutic armamentarium for autoimmune diseases and transplantation. Annu Rev Med 58 (2007) 347-358
3. Sugiyama H., McCormick T.S., Cooper K.D., and Korman N.J. Alefacept in the treatment of psoriasis. Clin Dermatol 26 (2008) 503-508
4. The CAMMS223 Trial Investigators. Alemtuzumab vs. interferon beta-1a in early multiple sclerosis. N Engl J Med 359 (2008) 1786-1801. While alemutuzumab treatment improved clinical manifestations of patients with RRMS and reduced corresponding brain MRI lesions, its use was associated with significant autoimmunity, most notably immune thrombocytopenic purpura.
5. Krupica Jr. T., Fry T.J., and Mackall C.L. Autoimmunity during lymphopenia: a two-hit model. Clin Immunol 120 (2006) 121-128
6. Chatenoud L., and Bluestone J.A. CD3-specific antibodies: a portal to the treatment of autoimmunity. Nat Rev Immunol 7 (2007) 622-632. An excellent review of the scientific rationale behind the use of CD3-specific antibodies in type 1 diabetes.
7. Keymeulen B., Vandemeulebroucke E., Ziegler A.G., Mathieu C., Kaufman L., Hale G., Gorus F., Goldman M., Walter M., Candon S., et al. Insulin needs after CD3-antibody therapy in new-onset type 1 diabetes. N Eng J Med 352 (2005) 2598-2608
8. Bisikirska B., Colgan J., Luban J., Bluestone J.A., and Herold K.C. TCR stimulation with modified anti-CD3 mAb expands CD8+ T cell population and induces CD8+CD25+ T regs. J Clin Invest 115 (2005) 2904-2913
9. Plevy S., Salzbergt B., van Assche G., Regueiro M., Hommes D., Sandborn W., Hanauer S., Targan S., Mayer L., Mahadevan U., et al. A phase I study of visilizumab, a humanized anti-CD3 monoclonal antibody, in severe steroid-refractory ulcerative colitis. Gastroenterology 133 (2007) 1414-1422
10. Bielekova B., Howard T., Packer A.N., Richert N., Blevins G., Ohayon J., Waldmann T.A., McFarland H.F., and Martin R. Effect of anti-CD25 antibody daclizimab in the inhibition of inflammation and stabilization of disease progression in multiple sclerosis. Arch Neurol 66 (2009) 483-489
11. Oh U., Blevins G., Griffith C., Richert N., Maric D., Lee C.R., McFarland H., and Jacobson S. Regulatory T cells are reduced during anti-CD25 antibody treatment of multiple sclerosis. Arch Neurol 66 (2009) 471-479
12. + regulatory T-cells. Diabetes 57 (2008) 2341-2347
13. Miller S.D., Turley D.M., and Podojil J.R. Antigen-specific tolerance strategies for the prevention and treatment of autoimmune disease. Nat Rev Immunol 7 (2007) 655-677. An excellent review of antigen-specific therapies and their scientific rationale across a range of autoimmune conditions.
14. The Diabetes Prevention Trial-Type 1 Study Group. Effects of oral insulin in relatives of patients with type 1 diabetes. Diabetes Care 28 (2005) 1068-1076
15. The Diabetes Prevention Trial-Type 1 Study Group. Effects of insulin in relatives of patients with type 1 diabetes mellitus. N Engl J Med 346 (2005) 1685-1691
16. Thrower S.L., James L., Hall W., Green K.M., Arif S., Allen J.S., Van-Krinks C., Lozanoska-Ochser B., Marquesini L., Brown S., et al. Proinsulin peptide immunotherapy in type 1 diabetes: report of a first-in-man phase I safety study. Clin Exp Immunol 155 (2008) 156-165
17. Gottleib P., Colman P.G., Kipnes M., Ratner R., Aroda V., Rendell M., Gerstman M., Zemel L., Dunn P., Hays R., et al. Interim results of a phase I/II clinical trial of a DNA plasma vaccine (BHT-3021) for type 1 diabetes. Presented at the 69th Annual Meeting of the American Diabetes Association. June 5-9; New Orleans, LA (2009)
18. Ludvigsson J., Faresjö M., Hjorth M., Axelsson S., Chéramy M., Pihl M., Vaarala O., Forsander G., Ivarsson S., Johansson C., et al. GAD treatment and insulin secretion in recent-onset type 1 diabetes. N Engl J Med 359 (2008) 1909-1920. The results of this trial represent a milestone in the efforts to develop an effective vaccine for the treatment of type 1 diabetes.
19. Warren K.G., Catz I., Ferenczi L.Z., and Krantz M.J. Intravenous synthetic peptide MBP8298 delayed disease progression in an HLA class II-defined cohort of patients with progressive multiple sclerosis: results a 24-month double-blind placebo-controlled clinical trial and 5 years of follow-up treatment. Eur J Neurol 13 (2006) 887-895
20. Bar-Or A., Vollmer T., Antel J., Arnold D., Bodner C.A., Campagnolo D., Gianettoni J., Jalili F., Kachuck N., Lapierre Y., et al. induction of antigen-specific tolerance in multiple sclerosis after immunization with DNA encoding myelin basic protein in a randomized, placebo-controlled phase 1/2 trial. Arch Neurol 64 (2007) 1407-1415
21. Yanaba K., Bouaziz J., Matsushita T., Magro C.M., St Clair E.W., and Tedder T.F. B-lymphocyte contributions to human autoimmune disease. Immunol Rev 223 (2008) 284-299. A comprehensive review of the role of B cells in the pathogenesis of human autoimmune disease, and the potential mechanisms of B cell directed therapies.
22. + B cells that demonstrate reciprocal effects on experimental allergic encephalomyelitis depending on whether they are active during the induction or progression of disease.
23. Franciotta D., Salvetti M., Lolli F., Serafini B., and Aloisi F. B cells and multiple sclerosis. Lancet Neurol 7 (2008) 852-858. A concise review highlighting the role of B cells in the pathogenesis of multiple sclerosis.
24. Hauser S.L., Waubant E., Arnold D.L., Vollmer T., Antel J., Fox R.J., Bar-Or A., Panzara M., Sarkar N., Agarwal S., et al. B-cell depletion with rituximab in relapsing-remitting multiple sclerosis. N Engl J Med 358 (2008) 676-688. This article describes the results of a randomized, placebo-controlled phase II clinical trial of rituximab therapy for relapsing-remitting multiple sclerosis that provides evidence for involvement of B cells in the pathogenesis of this disease.
25. Bar-Or A., Calabresi P.A., Arnold D., Markowitz C., Shafer S., Kasper L.H., Waubant E., Gazda S., Fox R.J., Panzara M., et al. Rituximab in relapsing-remitting multiple sclerosis: a 72-week, open-label, phase I trial. Ann Neurol 63 (2008) 395-400
26. Joly P., Mouquet H., Roujeau J.-C., D'Incan M., Gilbert D., Jacquot S., Gougeon M.-L., Bedane C., Muller R., Dreno B., et al. A single cycle of rituximab for the treatment of severe pemphigus. N Engl J Med 357 (2007) 545-552. This prospective clinical trial constitutes the best evidence for the clinical efficacy and safety of rituximab therapy for pemphigus vulgaris.
27. Pescovitz M, Greenbaum C, Becker D, Gitelman S, Goland R, Gottleib P, Marks J, McGee P, Moran A, Raskin P et al.: Rituximab, B-lymphocyte depletion and preservation of beta-cell function. N Engl J Med 2009; in press.
28. Carson K.R., Evens A.M., Richey E.A., Habermann T.M., Focosi D., Seymour J.F., Laubach J., Bawn S.D., Gordon L.I., Winter J.N., et al. Progressive multifocal leukoencephalopathy after rituximab therapy in HIV-negative patients: a report of 57 cases from the Research on Adverse Drug Events and Reports project. Blood 113 (2009) 4834-4840. This article describes 57 cases of PML following rituximab therapy. Most o the patients had lymphoproliferative disorders and had been treated with multiagent chemotherapy in addition to rituximab. However, one patient with autoimmune hemolytic anemia developed PML after treatment with corticosteroids and rituximab, and another patient with an autoimmune pancytopenia developed PML after treatment with corticosteroids, azathioprine, and rituximab.
29. Burge D.J., Bookbinder S.A., Kivitz A.J., Fleischmann R.M., Shu C., and Bannink J. Pharmacokinetic and pharmacodynamic properties of TRU-015, a CD20-directed small modular immunopharmaceutical protein therapeutic, in patients with rheumatoid arthritis: a phase I, open-label, dose-escalation study. Clin Ther 30 (2008) 1806-1816
30. Dörner T., Kaufmann J., Wegener W.A., Teoh N., Goldenberg D.M., and Burmester G.R. Initial clinical trial of epratuzumab (humanized anti-CD22 antibody) for immunotherapy of systemic lupus erythematosus. Arthritis Res Ther 8 (2006) R74 10.1186/ar1942
31. Steinfeld S.D., Tant L., Burmester G.R., Toeh N.K., Wegener W.A., Goldenberg D.M., and Pradier O. Epratuzumab (humanised anti-CD22 antibody) in primary Sjögren's syndrome: an open-label phase I/II study. Arthritis Res Ther 8 (2006) R129 10.1186/ar2018
32. Cardiel M.H., Tumlin J.A., Furie R.A., Wallace D.J., John T., Linnik M.D., and and the LJP 394-90-09 Investigator Consortium. Abetimus sodium for renal flare in systemic lupus erythematosus. Results of a randomized, controlled phase III trial. Arthritis Rheum 58 (2008) 2470-2480
33. Mackay F., Silveira P.A., and Brink R. B cells and the BAFF/APRIL axis: fast forward on autoimmunity and signaling. Curr Opin Immunol 19 (2007) 327-336
34. Furie R., Stohl W., Ginzler E.M., Becker N.M., Mishra N., Chatham W., Merrill J.T., Weinstein A., McCune W.J., Zhong J., et al. Biologic activity and safety of belimumab, a neutralizing anti-B-lymphocyte stimulator (BLyS) monoclonal antibody: a phase I trial in patients with systemic lupus erythmatosus. Arthritis Res Ther 8 (2008) R109 10.1186/ar2506
35. Human Genome Sciences and GlaxoSmithKline Announce Positive Phase 3 Study Results for Benlysta™ (http://www.hgsi.com/latest/human-genome-sciences-and-glaxosmithkline-announce-positive-phase-3-study-results-for-benl-2.html, last accessed August 27, 2009).
36. Dall'Era M., Chakravarty E., Wallace D., Genovese M., Weisman M., Kavanaugh A., Kalunian K., Dhar P., Vincent E., Penna-Rossi C., et al. Reduced B lymphocyte and immunoglobulin levels after atacicept treatment in patients with systemic lupus erythematosus. Results of a multicenter, phase 1b, double-blind, placebo-controlled, dose-escalating trial. Arthritis Rheum 56 (2007) 4142-4150
37. Tak P.P., Thurlings R.M., Rossier C., Nestorov I., Dimic A., Mircetic V., Rischmueller M., Nasonov E., Shmidt E., Emery P., and Munafo A. Atacicept in patients with rheumatoid arthritis. Results of a multicenter, phase 1b, double-blind, placebo-controlled, dose-escalating trial. Arthritis Rheum 58 (2008) 61-72
38. MacKay C.R. Moving targets: cell migration inhibitors as new anti-inflammatory therapies. Nat Immunol 9 (2008) 988-998. A state-of-the-art review of cell migration inhibitors in pharmaceutical development, including thoughtful commentary about the challenges in targeting chemoattractant receptors.
39. Ransohoff R. Natalizumab for multiple sclerosis. N Engl J Med 356 (2007) 2622-2629. An excellent summary of the clinical evidence supporting the use of natalizumab for the treatment of multiple sclerosis.
40. Targan S.R., Feagan B.G., Fedorak R.N., Lashner B.A., Panaccione R., Present D.H., Spehlmann M.E., Rutgeerts P.J., Tulassay Z., Volfova M., et al. Natalizumab for the treatment of active Crohn's disease. Results of the ENCORE trial. Gastroenterology 132 (2007) 1672-1683
41. Hartung H.-P. New cases of progressive multifocal leukoencephalopathy after treatment with natalizumab. Lancet Neurol 8 (2009) 28-31
42. Kappos L., Antel J., Comi G., Montalban X., O'Connor P., Polman C.H., Haas T., Korn A.A., Karlsson G., Radue E.W., and for the FTY720 D2201 Study Group. Oral fingolimod (FTY720) for relapsing multiple sclerosis. N Engl J Med 55 (2006) 1124-1140. Seminal results providing proof-of-concept for the clinical efficacy and safety of oral fingolimod therapy for multiple sclerosis.
43. O'Connor P., Comi G., Montalban X., Antel J., Radue E.W., de Vera A., Pohlmann H., Kappos L., and for the FTY720 D2201 Study Group. Oral fingolimod (FTY720) in multiple sclerosis. Two-year results of a phase II extension study. Neurology 72 (2009) 73-79
44. Plushner S.L. Tocilizumab: an interleukin-6 receptor inhibitor for the treatment of rheumatoid arthritis. Ann Pharmacother 42 (2008) 1660-1668
45. Rose-John S., Scheller J., Elson G., and Jones S.A. Interleukin-6 biology is coordinated by membrane-bound and soluble receptors: role in inflammation and cancer. J Leukoc Biol 80 (2006) 227-236
46. Genovese M.C., McKay J.D., Nasonov E.L., Mysler E.F., da Silva N.A., Alecock E., Woodworth T., and Gomez-Reino J.J. Interleukin-6 receptor inhibition with tocilizumab reduces disease activity in rheumatoid arthritis with inadequate response to disease-modifying antirheumatic drugs. Arthritis Rheum 58 (2008) 2968-2980
47. Smolen J.S., Beaulieu A., Rubbert-Roth A., Ramos-Remus C., Rovensky J., Alecock E., Woodworth T., Alten R., and for the OPTION Investigators. Effect of interleukin-6 receptor inhibition with tocilizumab in patients with rheumatoid arthritis (OPTION study): a double-blind, placebo-controlled, randomized trial. Lancet 371 (2008) 987-997. Among the large multicenter trials showing that tocilizumab benefits patients with rheumatoid arthritis.
48. Yokota S., Imagawa T., Mori M., Miyamae T., Aihaa Y., Takei S., Iwata N., Umebayashi H., Murata T., Miyoshi M., et al. Efficacy and safety of tocilizumab in patients with systemic-onset juvenile idiopathic arthritis: a randomized, double-blind, placebo-controlled, withdrawal phase III trial. Lancet 371 (2008) 998-1006. This trial deserves mention because it is one of the few examples where a novel therapy for a relatively uncommon disease has been rigorously tested in children.
49. 17 axis: therapeutic targets for autoimmune inflammation. Curr Opin Immunol 18 (2006) 670-675
50. Krueger G.G., Langley R.G., Leonardi C., Yeilding N., Guzzo C., Wang Y., Dooley L.T., Lebwohl M., and for the CNTO 1275 Psoriasis Study Group. A human interlukin-12/23 monoclonal antibody for the treatment of psoriasis. N Engl J Med 356 (2007) 580-592. The first randomized, placebo-controlled trial to show that ustekinumab is effective for the treatment of psoriasis.
51. Leonardi C.L., Kimball A.B., Papp K.A., Yielding N., Guzzo C., Wang Y., Li S., Dooley L.T., Gordon K.B., and for the PHOENIX 1 study investigators. Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 76-week results from a randomized, double-blind, placebo-controlled trial (PHOENIX 1). Lancet 371 (2008) 1665-1674. Results from a large multicenter, placebo-controlled trial confirming the efficacy and safety of ustekinumab for the treatment of psoriasis.
52. Leonardi C.L., Langley R.G., Lebwohl M., Krueger G.G., Szapary P., Yielding N., Guzzo C., Hsu M.-C., Wang Y., Li S., et al., for the PHOENIX 2 study investigators. Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 52-week results from a randomized, double-blind, placebo-controlled trial (PHOENIX 2). Lancet 371 (2008) 1675-1684. Evidence suggesting that shortening the dosage interval for ustekinumab 90 mg from every 12 to 8 weeks, which may improve efficacy in some patients with an inadequate treatment response.
53. Gottlieb A., Menter A., Mendelsohn A., Shen Y.-K., Li S., Guzzo C., Fretzin S., Kunyntz R., and Kavanaugh A. Ustekinumab, a human interleukin 12/23 monoclonal antibody, for psoriatic arthritis: randomized, double-blind, placebo-controlled, crossover trial. Lancet 373 (2009) 633-640
54. Sandborn W.J., Feagan B.G., Fedorak R.N., Scherl E., Fleisher M.R., Katz S., Johanns J., Blank M., Rutgeerts P., and for the Ustekinumab Crohn's Disease Study Group. A randomized trial of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with moderate-to-severe Crohn's disease. Gastroenterology 135 (2008) 1130-1141
55. Kimball A.B., Gordon K.B., Langley R.G., Menter A., Chartash E.K., Valdes J., and for the ABT-874 Psoriasis Study Investigators. Safety and Efficacy of ABT-874, a full human interleukin 12/23 monoclonal antibody, in the treatment of moderate to severe chronic plaque psoriasis. Results of a randomized, placebo-controlled, phase 2 trial. Arch Dermatol 144 (2008) 200-207
56. Zheng Y., Danilenko D.M., Valdez P., Kasman I., Eastham-Anderson J., Wu J., and Ouyang W. Interleukin-22, a TH17 cytokine, mediates IL-23-induced dermal inflammation and acanthosis. Nature 445 (2007) 648-651
57. Ma H.-K., Liang S., Li J., Napierata L., Brown T., Benoit S., Senices M., Gill D., Dunussi-Joannopoulos K., Collins M., et al. IL-22 is required for Th17 cell-mediated pathology in a mouse model of psoriasis-like skin inflammation. J Clin Invest 118 (2008) 597-607
58. Cohen S.B., Cheng T.-T., Chindalore V., Damjanov N., Burgos-Vargas R., DeLora P., Zimany K., Travers H., and Caulfield J.P. Evaluation of the efficacy and safety of pamapimod, a p38 MAP kinase inhibitor, in a double-blind, methotrexate-controlled study of patients with active rheumatoid arthritis. Arthritis Rheum 60 (2009) 335-344
59. Kremer J.M., Bloom B.J., Breedveld F.C., Coombs J.H., Fletcher M.P., Gruben D., Krishnaswami S., Burgos-Vargas R., Wilkinson B., Zerbini C.A., and Zwillich S.H. The safety and efficacy of a JAK inhibitor in patients with active rheumatoid arthritis. Results of a double-blind, placebo-controlled phase IIa trial of three dosage levels of CP-690,550 versus placebo. Arthritis Rheum 60 (2009) 1895-1905. Oral JAK inhibitors are likely to make their way into clinical practice within a few years. These small molecular entities along with others may revolutionize the treatment of chronic inflammatory diseases.
60. Weinblatt M.E., Kavanaugh A., Burgos-Vargas R., Dikranian A.H., Medrano-Ramirez G., Morales-Torres J.L., Murphy F.T., Musser T.K., Straniero N., Vincente-Gonzales A.V., and Grossbard E. Treatment of rheumatoid arthritis with a Syk kinase inhibitor. A twelve-week, randomized, placebo-controlled trial. Arthritis Rheum 58 (2008) 3309-3318. Among the first of a new generation of kinase inhibitors, with early results suggesting clinical efficacy for the treatment of RA.
61. R788 in TASKi3 Clinical Trial Does Not Meet Efficacy Endpoints in RA Patients Who Had Previously Failed Biologic Therapies-Results Incongruent (http://news.prnewswire.com/DisplayReleaseContent.aspx?ACCT=104&STORY=/www/story/07-23-2009/0005065480&EDATE=, last accessed August 27, 2009).
62. Paniagua R.T., Sharpe O., Ho P.P., Chan S.M., Chang A., Higgins J.P., Tomooka B.H., Thomas F.M., Song J.J., Goodman S.B., et al. Selective tyrosine kinase inhibition by imatinib mesylate for the treatment of autoimmune arthritis. J Clin Invest 116 (2006) 2633-2642
63. Louvet C., Szot G.L., lang J., Lee M.R., Martinier N., Bollag G., Zhu S., Weiss A., and Bluestone J.A. Tyrosine kinase inhibitors reverse type 1 diabetes in nonobese diabetic mice. Proc Natl Acad Sci U S A 105 (2008) 18895-18900
64. Quintάs-Cardama A., Kantarjian H., and Cortes J. Flying under the radar: the new wave of BCR-ABL inhibitors. Nat Rev Drug Disc 6 (2007) 834-848
65. Wehling M. Assessing the translatability of drug projects: what needs to be scored to predict success?. Nat Rev Drug Disc 8 (2009) 541-546
66. Muchamuel T., Basler M., Aujay M.A., Suzuki E., Kalim K.W., Lauer C., Sylvain C., Ring E., Shields J., Jiang J., et al. A selective inhibitor of the immunoporteasome subunit LMP7 blocks cytokine production and attenuates progression of experimental arthritis. Nat Med 15 (2009) 781-788. This study describes a unique role for LMP7 in regulating pathogenic immune responses.
67. Jia J., Zhu F., Ma X., Cao Z.W., Li Y.X., and Chen Y.Z. Mechanisms of drug combinations: interactions and perspectives. Nat Rev Drug Disc 8 (2009) 111-128
68. Kitano H. A robustness-based approach to systems-oriented drug design. Nat Rev Drug Disc 6 (2007) 202-210
69. Rose-John S., Waetig G.H., Scheller J., Grotzinger J., and Seegart D. The IL-6/sIL-6R complex as a novel target for therapeutic approaches. Exp Opin Ther Targets 11 (2007) 613-624