Skip to main content
SpringerLink
Log in

Monoclonal Antibody Therapy in Rheumatoid Arthritis

  • Review Article
  • Disease Treatment Review
  • Published:
Clinical Immunotherapeutics Aims and scope Submit manuscript

Summary

Rheumatoid arthritis is a chronic destructive joint disease, mediated by autoreactive immune cells. These cells, which express particular membrane antigens and release proliferative and catabolic cytokines, can be targeted by monoclonal antibodies. Potential targets for specific immune intervention with monoclonal antibodies are lymphocyte membrane antigens (CD3, CD4, CD5, CD7, CDw52, interleukin-2 receptor, T cell receptor, and adhesion molecules), human leucocyte antigen (HLA) class II antigens, and cytokines (interleukin-1, tumour necrosis factor-α and interleukin-6).

Administration of rodent antibodies may cause immune reactions. To minimise these, it is preferable to use humanised (chimaeric or complementarity-determining region-grafted) antibodies.

A final judgement on the clinical usefulness of these monoclonal antibodies can only be made after more extensive experience. In particular, there is an urgent need for double-blind controlled trials.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Waldmann H, Cobbold S. The use of monoclonal antibodies to achieve immunological tolerance. Immunol Today 1993; 14: 247–51

    Article  PubMed  CAS  Google Scholar 

  2. Ortho Multicenter Transplantation Group. A randomized clinical trial of OKT3 monoclonal antibody for acute rejection of cadaveric renal transplants. N Engl J Med 1985; 313: 337–42

    Article  Google Scholar 

  3. Abramowicz D, Schandrene L, Goldman M, et al. Release of TNF, IL-2 and IFN-gamma in serum after injection of OKT3 monoclonal antibody in kidney transplant recipients. Transplantation 1989; 47: 606–8

    Article  PubMed  CAS  Google Scholar 

  4. Goronzy J, Weyand CM, Fathman CG. Long-term humoral unresponsiveness in vivo, induced by treatment with monoclonal antibody against L3T4. J Exp Med 1986; 164: 911–25

    Article  PubMed  CAS  Google Scholar 

  5. Benjamin RJ, Qin SX, Wise MP, et al. Mechanisms of monoclonal antibody-facilitated tolerance induction: a possible role for the CD4 (L3T4) and CD11a (LFA-1) molecules in self-non-self discrimination. Eur J Immunol 1988; 18: 1079–88

    Article  PubMed  CAS  Google Scholar 

  6. Cobbold SOP, Jayasuriya A, Nash A, et al. Therapy with monoclonal antibodies by elimination of T-cell subsets in vivo. Nature 1984; 312: 548–51

    Article  PubMed  CAS  Google Scholar 

  7. Hafler DA, Weiner HL. Immunosuppression with monoclonal antibodies in multiple sclerosis. Neurology 1988; 38 (Suppl.): 42–7

    Article  PubMed  CAS  Google Scholar 

  8. Hafler DA, Ritz J, Schlossman SF, et al. Anti-CD4 and anti-CD2 monoclonal antibody infusions in subjects with multiple sclerosis: immunosuppressive effects and human anti-mouse responses. J Immunol 1988; 141: 131–8

    PubMed  CAS  Google Scholar 

  9. Herzog CH, Walker CH, Pichler W, et al. Monoclonal anti-CD4 in arthritis [letter]. Lancet 1987; 2: 1461–2

    Article  PubMed  CAS  Google Scholar 

  10. Breedveld FC, De Vries RRP. Anti-CD4 antibodies in rheumatoid arthritis [editorial]. Clin Exp Rheumatol 1992; 10: 325–6

    PubMed  CAS  Google Scholar 

  11. Horneff G, Winkler T, Kalden JR, et al. Human anti-mouse antibody response induced by anti-CD4 monoclonal antibody therapy in patients with rheumatoid arthritis. Clin Immunol Immunopathol 1991; 59: 89–103

    Article  PubMed  CAS  Google Scholar 

  12. Herzog C, Walker C, Muller W, et al. Anti-CD4 antibody treatment of patients with rheumatoid arthritis: I. Effect on clinical course and circulating T cells. J Autoimmun 1989; 2: 627–42

    Article  PubMed  CAS  Google Scholar 

  13. Goldberg D, Morel P, Chatenoud L, et al. Immunological effects of high dose administration of anti-CD4 antibody in rheumatoid arthritis patients. J Autoimmun 1991; 4: 617–30

    Article  PubMed  CAS  Google Scholar 

  14. Horneff G, Burmester GR, Emmrich F, et al. Treatment of rheumatoid arthritis with an anti-CD4 monoclonal antibody. Arthritis Rheum 1991; 34: 129–40

    Article  PubMed  CAS  Google Scholar 

  15. Reiter C, Kakavand B, Rieber EP, et al. Treatment of rheumatoid arthritis with monoclonal CD4 antibody M-T151: clinical results and immunopharmacological effects in an open study, including repeated administration. Arthritis Rheum 1991; 34: 525–36

    Article  PubMed  CAS  Google Scholar 

  16. Wendling D, Wijdenes J, Racadot E, et al. Therapeutic use of monoclonal anti-CD4 antibody in rheumatoid arthritis. J Rheumatol 1991; 18: 325–7

    PubMed  CAS  Google Scholar 

  17. Didri C, Portalès P, Andary M, et al. Treatment of rheumatoid arthritis with monoclonal anti-CD4 antibodies: clinical results. Arthritis Rheum 1991; 34 (Suppl.): S92

    Google Scholar 

  18. van der Lubbe PA, Reiter C, Riethmuller G, et al. Treatment of rheumatoid arthritis with chimeric CD4 monoclonal antibody. Arthritis Rheum 1991; 34 (Suppl.): S89

    Article  Google Scholar 

  19. Racadot E, Wijdenes J, Wendling D. Immunological follow-up of 17 patients with rheumatoid arthritis treated in vivo with an anti-T CD4+ monoclonal antibody (B-F5). Clin Exp Rheumatol 1992; 10: 365–74

    PubMed  CAS  Google Scholar 

  20. Moreland LW, Bucy RP, Tilden A, et al. Use of a chimeric monoclonal anti-CD4 antibody in patients with refractory rheumatoid arthritis. Arthritis Rheum 1993; 36: 307–18

    Article  PubMed  CAS  Google Scholar 

  21. Burmester GR, Horneff G, Emmrich F. Intervention with immunomodulatory agents: monoclonal antibody therapy. Baillieres Clin Rheumatol 1992; 6: 415–34

    Article  PubMed  CAS  Google Scholar 

  22. Carteron NL, Schimenti CL, Wofsy D. Treatment of murine lupus with F(ab′)2 fragments of monoclonal antibody to L3T4. J Immunol 1989; 142: 1470–5

    PubMed  CAS  Google Scholar 

  23. Gutstein NI, Wofsy D. Administration of F(ab′)2 fragments of monoclonal antibody to L3T4 inhibits humoral immunity in mice without depleting L3T4+ cells. J Immunol 1986; 137: 3414–9

    PubMed  CAS  Google Scholar 

  24. Shizuru JA, Seydel KB, Flavin TF, et al. Induction of donor specific unresponsiveness to cardiac allografts in rats by pretransplant anti-CD4 monoclonal antibody therapy. Transplantation 1990; 50: 366–73

    Article  PubMed  CAS  Google Scholar 

  25. Mazerolles F, Auffray C, Fischer A. Down regulation of T-cell adhesion by CD4. Hum Immunol 1991; 31: 40–6

    Article  PubMed  CAS  Google Scholar 

  26. Cole JA, McCarthy SA, Rees MA, et al. Cell surface comodulation of CD4 and T cell receptor by anti-CD4 monoclonal antibody. J Immunol 1989; 143: 397–402

    PubMed  CAS  Google Scholar 

  27. Israelski DM, Araujo FG, Conley FK, et al. Treatment with anti-L3T4 (CD4) monoclonal antibody reduces the inflammatory response in toxoplasmic encephalitis. J Immunol 1989; 142: 954–8

    PubMed  CAS  Google Scholar 

  28. Wilde DB, Marrack P, Kappler J, et al. Evidence implicating L3T4 in class II MHC antigen reactivity: monoclonal antibody GK1.5 (anti-L3T4a) blocks class II MHC antigen-specific proliferation, release of lymphokines and binding by cloned murine helper T lymphocyte lines. J Immunol 1983; 131: 2078–83

    Google Scholar 

  29. Plater-Zyberc C, Maini RN, Lam K, et al. A rheumatoid arthritis B cell subset expresses a phenotype similar to tat in chronic lymphocytic leukemia. Arthritis Rheum 1985; 28: 971–6

    Article  Google Scholar 

  30. Jarvis JN, Kaplan J, Fine N. Increase in CD5+ B cells in juvenile rheumatoid arthritis. Arthritis Rheum 1992; 35: 204–7

    Article  PubMed  CAS  Google Scholar 

  31. Dauphinee M, Tovar Z, Talal N. B cell expressing CD5 are increased in Sjogren’s syndrome. Arthritis Rheum 1988; 31: 642–7

    Article  PubMed  CAS  Google Scholar 

  32. Strand V, Fishwild D, XOMA Rheumatoid Arthritis Investigators Group. Treatment of rheumatoid arthritis with an anti-CD5 immunoconjugate: clinical and immunologic findings and preliminary results of re-treatment. Arthritis Rheum 1990; 33 (Suppl.): S25

    Google Scholar 

  33. Cush JJ, Nichols LA, Strand V, et al. Treatment of rheumatoid arthritis patients with an anti-CD5 immunoconjugate. Arthritis Rheum 1991; 34 (Suppl.): S159

    Article  Google Scholar 

  34. Cannon GW, Marble DA, Griffiths MM, et al. Immunologic assessment during treatment of rheumatoid arthritis with anti-CD5 immunoconjugate. Arthritis Rheum 1991; 34 (Suppl.): S157

    Google Scholar 

  35. Strand V, Lipsky PE, Cannon G, et al. Effects of administration of an anti-CD5 plus immunoconjugate in rheumatoid arthritis: results of phase II studies. Arthritis Rheum 1993; 36: 620–30

    Article  PubMed  CAS  Google Scholar 

  36. Verwilghen J, Kingsley GH, Ceuppens JL, et al. Inhibition of synovial fluid T cell proliferation by anti-CD5 monoclonal antibodies: a potential mechanism for their immunotherapeutic action in vivo. Arthritis Rheum 1992; 35: 1445–51

    Article  PubMed  CAS  Google Scholar 

  37. Poulter LW, Duke O, Panayi GS, et al. Activated T lymphocytes of the synovial membrane in rheumatoid arthritis and other arthropathies. Scand J Immunol 1985; 22: 683–90

    Article  PubMed  CAS  Google Scholar 

  38. Kirkham BW, Pitzalis C, Kingsley GH, et al. Monoclonal antibody therapy in rheumatoid arthritis: the clinical and immunological effects of a CD7 monoclonal antibody. Br J Rheumatol 1991; 30: 459–63

    Article  PubMed  CAS  Google Scholar 

  39. Kirkham BW, Thien F, Pelton BK, et al. Chimeric CD7 monoclonal antibody therapy in rheumatoid arthritis. J Rheumatol 1992; 19: 1348–52

    PubMed  CAS  Google Scholar 

  40. Isaacs J, Watts RA, Hazleman BL, et al. Humanised monoclonal antibody therapy for rheumatoid arthritis. Lancet 1992; 340: 748–52

    Article  PubMed  CAS  Google Scholar 

  41. Poynton CH, Mort D, Maughan TS. Adverse reactions to Campath-1H monoclonal antibody. Lancet 1993; 341: 1037

    Article  PubMed  CAS  Google Scholar 

  42. Kupiec-Weglinski JW, Diamantstein T, Tilney NL, et al. Therapy with monoclonal antibody to IL-2 receptor spares suppressor T cells and prevents or reverses acute allograft rejection in rats. Proc Natl Acad Sci USA 1986; 83: 2624–7

    Article  PubMed  CAS  Google Scholar 

  43. Kelley VE, Gaulton GN, Hattori M, et al. Anti-IL-2 receptor antibody suppresses murine diabetic insulitis and lupus nephritis. J Immunol 1988; 140: 59–61

    PubMed  CAS  Google Scholar 

  44. Kyle V, Coughlan RJ, Tighe H, et al. Beneficial effect of Mab to IL-2 receptor on activated T cells in rheumatoid arthritis. Ann Rheum Dis 1989; 48: 428–9

    Article  PubMed  CAS  Google Scholar 

  45. Acha-Orbea H, Mitchell DJ, Timmermann L, et al. Limited heterogeneity of T cell receptors from lymphocytes mediating autoimmune encephalomyelitis allows specific immune intervention. Cell 1988; 54: 263–73

    Article  PubMed  CAS  Google Scholar 

  46. Jasin HE, Lightfoot E, Davis LS, et al. Amelioration of antigen-induced arthritis in rabbits treated with monoclonal antibodies to leukocyte adhesion molecules. Arthritis Rheum 1992; 35: 541–9

    Article  PubMed  CAS  Google Scholar 

  47. Kavanaugh A, Nichols L, Lipsky P. Treatment of refractory rheumatoid arthritis with an anti-CD54 (ICAM-1) monoclonal antibody. Arthritis Rheum 1992; 35 (Suppl.): S43

    Article  Google Scholar 

  48. Kavanaugh A, Norris S, Rothlein R, et al. Pharmacokinetic analysis of rheumatoid arthritis patients treated with an anti-CD54 (ICAM-1) monoclonal antibody. Arthritis Rheum 1992; 35 (Suppl.): S106

    Article  Google Scholar 

  49. Arend WP, Dayer JM. Cytokines and cytokine inhibitors or antagonists in rheumatoid arthritis. Arthritis Rheum 1990; 33: 305–15

    Article  PubMed  CAS  Google Scholar 

  50. Saklatvala J. Regulation of chondrocytes by cytokines. In: Adolphe, M, editor. The biological regulation of chondrocytes. Boca Raton: CRC Press, 1992: 191–204

    Google Scholar 

  51. Brennan FM, Chantry D, Jackson A, et al. Inhibitory effect of tumour necrosis factor alpha antibodies on interleukin 1 in rheumatoid arthritis. Lancet 1989; 2: 244–7

    Article  PubMed  CAS  Google Scholar 

  52. Williams RO, Feldmann M, Maini RN. Anti-tumor necrosis factor ameliorates joint disease in murine collagen-induced arthritis. Proc Natl Acad Sci USA 1992; 89: 9784–8

    Article  PubMed  CAS  Google Scholar 

  53. Piguet PF, Grau GE, Vesin C, et al. Evolution of collagen arthritis in mice is arrested by treatment with anti-tumor necrosis factor (TNF) antibody or a recombinant soluble TNF receptor. Immunology 1992; 77: 510–4

    PubMed  CAS  Google Scholar 

  54. Feldmann M, Elliott M, Brennan F, et al. TNF-alpha as a therapeutic target in RA. Clin Rheumatol 1993; 12: 101

    Google Scholar 

  55. Houssiau FA, Devogelaer JP, Van Damme J, et al. Interleukin-6 in synovial fluid and serum of patients with rheumatoid arthritis and other inflammatory arthritides. Arthritis Rheum 1988; 31: 784–88

    Article  PubMed  CAS  Google Scholar 

  56. Miltenburg AMM, Van Laar JM, De Kuiper R, et al. Interleukin-6 activity in paired samples of synovial fluid. Br J Rheumatol 1991; 30: 186–9

    Article  PubMed  CAS  Google Scholar 

  57. Madhok R, Beaton A, Smith J, et al. The effect of second line drugs on serum interleukin 6 levels in RA [abstract]. Arthritis Rheum 1990; 33: S154

    Article  Google Scholar 

  58. Wendling D, Racadot E, Wijdenes J. Treatment of severe rheumatoid arthritis by anti-interleukin 6 monoclonal antibody. J Rheumatol 1993; 20: 259–62

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Rheumatology, University Hospital Ghent, De Pintelaan 185, B-9000, Ghent, Belgium

    Filip De Keyser, Dirk Elewaut, Anne-Marie Malfait & Eric Veys

Authors
  1. Filip De Keyser
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Dirk Elewaut
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Anne-Marie Malfait
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Eric Veys
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

De Keyser, F., Elewaut, D., Malfait, AM. et al. Monoclonal Antibody Therapy in Rheumatoid Arthritis. Clin. Immunother. 1, 148–156 (1994). https://doi.org/10.1007/BF03258500

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03258500

Keywords

Search

Navigation