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Antibodies for Inflammatory Disease

Effector Cells
  • Richard Smith
Part of the Methods in Molecular Medicine book series (MIMM, volume 40)

Abstract

Their inherent specificity makes antibodies attractive immunotherapeutic agents. Definition of appropriate therapeutic strategies requires parallel identification of potential target molecules and the immunotherapeutic mechanisms to be recruited by antibodies targeting these molecules. Regardless of the target antigen, antibodies may modify immune responses by:
  1. 1.

    Killing target cells (cytotoxic or depleting antibodies);

     
  2. 2.

    Blocking molecular interactions;

     
  3. 3.

    Modulating target molecules from the surface of cells; or

     
  4. 4.

    Modifying cell function as a consequence of signal transduction by ligated molecules.

     

Keywords

Experimental Autoimmune Encephalomyelitis Major Histocompatibility Complex Class Tolerance Induction Therapeutic Antibody Inflammatory Autoimmune Disease 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    Chambers, C. A. and Alison, J. P. (1997) Co-stimulation in T cell responses. Curr. Opin. Immunol. 9, 396–404.CrossRefPubMedGoogle Scholar
  2. 2.
    Lenschow, D. J., Walunas, T. L., et al. (1996) CD28/B7 system of T cell costimulation. Ann. Rev. Immunol. 14, 233–258.CrossRefGoogle Scholar
  3. 3.
    Saito, T. (1998) Negative regulation of T cell activation. Curr. Opin. Immunol. 10, 313–321.CrossRefPubMedGoogle Scholar
  4. 4.
    Grewal, I. S., Foellmer, H. G., et al. (1996) Requirement for CD40 ligand in costimulation induction, T cell activation and experimental allergic encephalo-myelitis. Science 273, 1864–1867.CrossRefPubMedGoogle Scholar
  5. 5.
    Yang, Y. and Wilson, J. M. (1996) CD40 ligand-dependent T cell activation: requirement of B7-CD28 signaling through CD40. Science 273, 1862–1864.CrossRefPubMedGoogle Scholar
  6. 6.
    Acha-Orbea, H., Mitchell, D. J., et al. (1988) Limited heterogeneity of T cell receptors from lymphocytes mediating autoimmune encephalomyelitis allows specific immune intervention. Cell 54, 263–273.CrossRefPubMedGoogle Scholar
  7. 7.
    Acha-Orbea, H. (1993) T-cell receptors in autoimmune disease, in Monoclonal Antibodies and Peptide Therapy in Autoimmune Diseases, vol. 59 (Bach, J.-F., ed.), Marcel Dekker, New York, pp. 131–142.Google Scholar
  8. 8.
    Aharoni, R., Teitelbaum, D., et al. (1991) Immunomodulation of experimental allergic encephalomyelitis by antibodies to the antigen-Ia complex. Nature 351, 147–150.CrossRefPubMedGoogle Scholar
  9. 9.
    Waldmann, T. A. (1993) The IL-2/IL-2 receptor system: a target for rational immune intervention. Immunol. Today 14, 264–269.CrossRefPubMedGoogle Scholar
  10. 10.
    Van Gelder, T. and Weimar, W. (1997) Potential of anti-interleukin-2 receptor monoclonal antibodies in solid organ transplantation. Biodrugs 8, 46–55.CrossRefGoogle Scholar
  11. 11.
    Kuttler, B., Kauert, C., et al. (1997) Anti-CD25/CsA therapy induced a CD4+ T cell-mediated tolerance in BB/OK rats. Immunobiology 197, 243.Google Scholar
  12. 12.
    Kyle, V., Coughlan, R. J., et al. (1989) Beneficial effect of monoclonal antibody to interleukin 2 receptor on activated T cells in rheumatoid arthritis. Ann. Rheumatic Dis. 48, 428–429.CrossRefGoogle Scholar
  13. 13.
    Kirkham, B., Pitzalis, C., et al. (1991) Monoclonal antibody therapy in rheumatoid arthritis: the clinical and immunological effects of a CD7 monoclonal antibody. Br. J. Rheumatol. 30, 459–463.CrossRefPubMedGoogle Scholar
  14. 14.
    Kirkham, B., Thien, F., et al. (1992) Chimeric CD7 monoclonal antibody therapy in rheumatoid arthritis. J. Rheumatol. 19, 1348–1352.PubMedGoogle Scholar
  15. 15.
    Williams, I. R. and Perry, L. L. (1985) A double determinant sandwich immu-noassay for quantitation of serum monoclonal anti-I-A antibody. J. Immunol. Methods 85, 279–294.CrossRefPubMedGoogle Scholar
  16. 16.
    Sayegh, M. H., Akalin, E., et al. (1995) CD28-B7 blockade after alloantigenic challenge in vivo inhibits Th1 cytokines but spares Th2. J. Exp. Med. 181, 1869–1874.CrossRefPubMedGoogle Scholar
  17. 17.
    Racke, M. K., Scott, D. E., et al. (1995) Distinct roles for B7-1 (CD-80) and B7-2 (CD-86) in the initiation of experimental allergic encephalomyelitis. J. Clin. Invest. 96, 2195–2203.CrossRefPubMedGoogle Scholar
  18. 18.
    Vladutiu, A. O. (1991) Treatment of autoimmune diseases with antibodies to class II major histocompatibility complex antigens. Clin. Immunol. Immunopathol. 61, 1–17.CrossRefPubMedGoogle Scholar
  19. 19.
    Fultz, M., Finkelman, F. D., et al. (1984) In vivo administration of anti-I-A antibody induces the internalization of B cell surface I-A and I-E without affecting the expression of surface immunoglobulin. J. Immunol. 133, 91–97.PubMedGoogle Scholar
  20. 20.
    Kruisbeek, A. M., Titus, J. A., et al. (1985) In vivo treatment with monoclonal anti-I-A antibodies: disappearance of splenic antigen-presenting cell function concomitant with modulation of splenic cell surface I-A and I-E antigens. J. Immunol. 134, 3605–3614.PubMedGoogle Scholar
  21. 21.
    Wade, W. F., Davoust, J., et al. (1993) Structural compartmentalization of MHC class II signaling function. Immunol. Today 14, 539–545.CrossRefPubMedGoogle Scholar
  22. 22.
    Scholl, P. R. and Geha, R. S. (1994) MHC class II signalling in B-cell activation. Immunol. Today 15, 418–422.CrossRefPubMedGoogle Scholar
  23. 23.
    Smith, R. M., Morgan, A., et al. (1994) Anti-class II MHC antibodies prevent and treat EAE without APC depletion. Immunology 83, 1–8.PubMedGoogle Scholar
  24. 24.
    Constant, S., Pfeiffer, C., et al. (1995) Extent of T cell receptor ligation can determine the functional differentiation of naive CD4+T cells. J. Exp. Med. 182, 1591–1596.CrossRefPubMedGoogle Scholar
  25. 25.
    Waldmann, H. and Cobbold, S. (1998) How do monoclonal antibodies induce tolerance? A role for infectious tolerance? Ann. Rev. Immunol. 16, 619–644.CrossRefGoogle Scholar
  26. 26.
    Lockwood, C. M., Thiru, S., et al. (1993) Long-term remission of intractable systemic vasculitis with monoclonal antibody therapy. Lancet 341, 1620–1622.CrossRefPubMedGoogle Scholar
  27. 27.
    Lockwood, C. M., Thiru, S., Stewart, S. (1996) Treatment of refractory Wegener’s granulomatosis with humanized monoclonal antibodies. QJM 89, 903–912.PubMedGoogle Scholar
  28. 28.
    Isaacs, J. D., Burrows, N., Wing, M., et al. (1997) Humanized anti-CD4 monoclonal antibody therapy of autoimmune and inflammatory disease. Clin. Exp. Immunol. 110, 158–166.CrossRefPubMedGoogle Scholar
  29. 29.
    Marrack, P., Endres, R., et al. (1983) The major histocompatibility complex-restricted antigen receptor on T-cells. II. Role of the L3T4 product. J. Exp. Med. 158, 1077–1091.CrossRefPubMedGoogle Scholar
  30. 30.
    Rudd, C. E., Trevillyan, J. M., et al. (1988) The CD4 receptor is complexed in detergent lysates to a protein-tyrosin kinase (pp58) from human T lymphocytes. Proc. Natl. Acad. Sci. USA 85, 190–194.CrossRefGoogle Scholar
  31. 31.
    Bartholomew, M., Brett, S., et al. (1995) Functional analysis of the effects of fully humanized anti-CD4 antibody on resting and activated human T cells. Immunology 85, 41–48.PubMedGoogle Scholar
  32. 32.
    Bank, I. and Chess, L. (1985) Perturbation of the T4 molecules transmits a negative signal in T-cells. J. Exp. Med. 162, 1294–1303.CrossRefPubMedGoogle Scholar
  33. 33.
    Isaacs, J. D. (1999) Does immunotherapy have a role? Questions and Uncertainties in Rheumatology (Bird, H. and Snaith, M., eds.), Blackwell Science, Oxford, UK, pp. 207–228.Google Scholar
  34. 34.
    Chatenoud, L., Thervet, E., et al. (1994) Anti-CD3 antibody induces long-term remission of overt autoimmunity in nonobese diabetic mice. Proc. Natl. Acad. Sci. USA 91, 123–127.CrossRefPubMedGoogle Scholar
  35. 35.
    Bolt, S., Routledge, E., et al. (1993) The generation of a humanized, non-mitogenic CD3 monoclonal antibody which retains in vitro immunosuppressive properties. Eur. J. Immunol. 23, 403–411.CrossRefPubMedGoogle Scholar
  36. 36.
    Routledge, E. G., Falconer, M. E., et al. (1995) The effect of aglycosylation on the immunogenicity of a humanized therapeutic CD3 monoclonal antibody. Transplantation 60, 847–853.PubMedGoogle Scholar
  37. 37.
    Harding, F. A., McArthur, J. G., et al. (1992) CD28-mediated signalling co-stimulates murine T cells and prevents induction of anergy in T-cell clones. Nature 356, 607–609.CrossRefPubMedGoogle Scholar
  38. 38.
    Jenkins, M. K. (1994) The ups and downs of T cell costimulation. Immunity 1, 443–446.CrossRefPubMedGoogle Scholar
  39. 39.
    Walunas, T. L., Lenschow, D. J., et al. (1994) CTLA-4 can function as a negative regulator of T cell activation. Immunity 1, 405–413.CrossRefPubMedGoogle Scholar
  40. 40.
    Karandikar, N. J., Vanderlugt, C. L., et al. (1996) CTLA-4: a negative regulator of autoimmune disease. J. Exp. Med. 184, 783–788.CrossRefPubMedGoogle Scholar
  41. 41.
    Larsen, C. P., Elwood, E. T., et al. (1996) Long-term acceptance of skin and cardiac allografts after blocking CD40 and CD28 pathways. Nature 381, 434–438.CrossRefPubMedGoogle Scholar
  42. 42.
    Khoury, S. J., Akalin, E., et al. (1995) CD28-B7 costimulatory blockade by CTLA4Ig prevents actively induced experimental autoimmune encephalomyeli-tis and inhibits Th1 but spares Th2 cytokines in the central nervous system. J. Immunol. 155, 4521–4524.PubMedGoogle Scholar
  43. 43.
    Akalin, E., Chandraker, A., et al. (1996) CD28-B7 T cell costimulatory blockade by CTLA4Ig in the rat renal allograft model. Transplantation 62, 1942–1945.CrossRefPubMedGoogle Scholar
  44. 44.
    Kuchroo, V. K., Das, M. P., et al. (1995) B7-1 and B7-2 costimulatory molecules activate differentially the Th1/Th2 developmental pathways: application to autoimmune disease therapy. Cell 80, 707–718.CrossRefPubMedGoogle Scholar
  45. 45.
    Lenschow, D. J., Ho, S. C., et al. (1995) Differential effects of anti-B7-1 and anti-B7-2 monoclonal antibody treatment on the development of diabetes in the nonobese diabetic mouse. J. Exp. Med. 181, 1145–1155.CrossRefPubMedGoogle Scholar
  46. 46.
    Vanderlugt, C. L., Karandikar, N. J., et al. (1997) Treatment with intact anti-B7-1 mAb during disease remission enhances epitope spreading and exacerbates relapses in R-EAE. J. Neuroimmunol. 79, 113–118.CrossRefPubMedGoogle Scholar
  47. 47.
    Lanier, L. L., O’Fallon, S., et al. (1995) CD80 (B7) and CD86 (B70) provide similar costimulatory signals for T cell proliferation, cytokine production, and generation of CTL. J. Immunol. 154, 97–105.PubMedGoogle Scholar
  48. 48.
    Ghiotto-Ragueneau, M., Battifora, M., et al. (1996) Comparison of CD28-B7.1 and B7.2 functional interaction in resting human T cells, Phosphatidylinositol 3-kinase association to CD28 and cytokine production. Eur. J. Immunol. 26, 34–41.CrossRefPubMedGoogle Scholar
  49. 49.
    Nunes, J. A., Battifora, M., et al. (1996) CD28 signal transduction pathways. A comparison of B7-1 and B7-2 regulation of the MAP kinases: ERK2 and Jun kinases. Mol. Immunol. 33, 63–70.CrossRefPubMedGoogle Scholar
  50. 50.
    Hirokawa, M., Kuroki, J., et al. (1996) Transmembrane signaling through CD80 (B7-1) induces growth arrest and cell spreading of human B lymphocytes accompanied by protein tyrosine phosphorylation. Immunol. Lett. 50, 95–98.CrossRefPubMedGoogle Scholar
  51. 51.
    Jeannin, P., Delneste, Y., et al. (1997) CD86 (B7-2) on human B cells. J. Biol. Chem. 25, 15,613–15,619.CrossRefGoogle Scholar
  52. 52.
    Freeman, G. J., Boussiotis, V. A., et al. (1995) B7-1 and B7-2 do not deliver identical costimulatory signals, since B7-2 but not B7-1 preferentially costimulates the initial production of IL-4. Immunity 2, 523–532.CrossRefPubMedGoogle Scholar

Copyright information

© Humana Press Inc. 2000

Authors and Affiliations

  • Richard Smith
    • 1
  1. 1.Academic Renal UnitSouthmead HospitalBristolUK

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