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Medical Applications of Leukocyte Surface Molecules—the CD molecules

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Abstract

Leukocytes are the cells of the Immune system and are centrally Involved in defense against Infection, in autoimmune disease, allergy, Inflammation, and in organ graft rejection. Lymphomas and leukemias are malignancies of leukocytes, and the Immune system Is almost certainly Involved In most other cancers. Each leukocyte expresses a selection of cell surface glycoproteins and glycolipids which mediate its Interaction with antigen, with other components of the Immune system, and with other tissues. It is therefore not surprising that the leukocyte surface molecules (CD molecules) have provided targets for diagnosis and therapy. Among the “celebrities” are CD20, a target for lymphoma therapeutic antibodies which earns $2 billion annually (and makes a significant difference to lymphoma patients), and CD4, the molecule used by the human immunodeficiency virus (HIV) as an entry portal into cells of the Immune system. This short review provides a background to the CD molecules and antibodies against them, and summarizes research, diagnostic, and therapeutic applications of antibodies against these molecules.

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References

  1. Mak TW, Saunders ME. (2006) The immune response: basic and clinical principles. Elsevier/Academic Press, Amsterdam.

    Google Scholar 

  2. Bernard AR, Boumsell L, Dausset J, Milstein C, Schlossmann SF, eds. (1984) Leucocyte typing: human leucocyte differentiation antigens detected by monoclonal antibodies. Springer, Berlin.

    Google Scholar 

  3. Reinherz EL, Haynes BF, Nadler L, Bernstein ID, eds. (1985) Leukocyte typing II. Springer, New York.

    Google Scholar 

  4. McMichael AJ, Beverley PCL, Cobbold S et al., eds. (1987) Leucocyte typing III: white cell differentiation antigens. Oxford University Press, Oxford.

    Google Scholar 

  5. Knapp W, Dorken B, Gilks W, Rieber EP, Schmidt RE, Stein H, von dem Borne AEGK, eds. (1989) Leucocyte typing IV: white cell differentiation antigens. Oxford University Press, Oxford.

    Google Scholar 

  6. Schlossman SF, Boumsell L, Gilks W et al., eds. (1995) Leucocyte typing V: white cell differentiation antigens. Oxford University Press, Oxford.

    Google Scholar 

  7. Kishimoto T, Kikutani H, von dem Borne AEGK et al., eds. (1997) Leucocyte typing VI: white cell differentiation antigens. Garland Publishing Inc., New York.

    Google Scholar 

  8. Mason D, Andre P, Bensussan A et al., eds. (2002) Leucocyte typing VII. Oxford University Press, Oxford.

    Google Scholar 

  9. Zola H, Swart B, Nicholson I et al. (2005) CD molecules 2005: human cell differentiation molecules. Blood 106:3123–6.

    Article  CAS  Google Scholar 

  10. Zola H, Swart BW. (2003) Human leucocyte differentiation antigens. Trends Immunol. 24:353–4.

    Article  CAS  Google Scholar 

  11. Zola H, Swart B, Nicholson I, Voss E. (2006, in press) Leukocyte and stromal cell molecules: the CD markers. Wiley, New York.

    Google Scholar 

  12. Nicholson I, Mavrangelos C, Fung K et al. (2005) Characterization of the protein composition of peripheral blood mononuclear cell microsomes by SDS-PAGE and mass spectrometry. J. Imm. Meths. 305:84–93.

    Article  CAS  Google Scholar 

  13. Vignali DAA. (2000) Multiplexed particle-based flow cytometric assays. J. Imm. Meths. 243:243–55.

    Article  CAS  Google Scholar 

  14. Liu W, Putnam A, Xu-yu Z et al. (2006) CD127 expression inversely correlates with FoxP3 and suppressive function of human CD4+T reg cells. J. Exp. Med. 203:1701–11.

    Article  CAS  Google Scholar 

  15. Garcia JF, Mollejo M, Fraga M. (2005). Large B-cell lymphoma with Hodgkin’s features. Histopathogy 47:101–10.

    Article  CAS  Google Scholar 

  16. Aubrey N, Muzard J, Peter JC, Rochat H, Goyffon M, Devaux C, Billiald P. (2004) Engineering of a recombinant Fab from a neutralizing IgG directed against scorpion neurotoxin AahI, and functional evaluation versus other antibody fragments. Toxicon 43:233–41.

    Article  CAS  Google Scholar 

  17. Feldmann M, Maini RN. (2001) Anti-TNFa therapy of rheumatoid arthritis: what have we learned? Ann. Rev. of Immun. 19:163–96

    Article  CAS  Google Scholar 

  18. Buske C, Weigert O, Dreyling M, Unterhalt M, Hiddemann W. (2006) Current status and perspective of antibody therapy in follicular lymphoma. Haematologica 91:104–12.

    CAS  PubMed  Google Scholar 

  19. Peterson JW, Comer JE, Noffsinger DM et al. (2006) Human monoclonal anti-protective antigen antibody completely protects rabbits and is synergistic with ciprofloxacin in protecting mice and guinea pigs against inhalation anthrax. Inf. and Immun. 74:1016–24.

    Article  CAS  Google Scholar 

  20. Gray JC, Johnson PW, Glennie MJ. (2006). Therapeutic potential of immunostimulatory monoclonal antibodies. Clin. Sci. 111:93–106.

    Article  CAS  Google Scholar 

  21. Kukreja A, Cost G, Marker J et al. (2002) Multiple immuno-regulatory defects in type-1 diabetes. J. Clin. Invest. 109:131–40.

    Article  CAS  Google Scholar 

  22. Lindley S, Dayan CM, Bishop A, Roep BO, Peakman M, Tree MIM. (2005) Defective suppressor function in CD4+CD25+ T-Cells from patients with Type 1 diabetes. Diabetes 54:92–9.

    Article  CAS  Google Scholar 

  23. Vitetta ES, Ghetie VF. (2006) Considering therapeutic antibodies. Science 313:308–9.

    Article  CAS  Google Scholar 

  24. Rastetter W, Molina A, White CA. (2004) Rituximab: expanding role in therapy for lymphomas and autoimmune diseases. Annu. Rev. Med. 55:477–503.

    Article  CAS  Google Scholar 

  25. Hagenbeek A. (2003) Radioimmunotherapy for NHL: experience of 90Y-ibritumomab tiuxetan in clinical practice. Leuk. Lymphoma 44 Suppl 4:S37–47.

    Article  CAS  Google Scholar 

  26. Vose JM. (2004) Bexxar: novel radioimmunotherapy for the treatment of low-grade and transformed low-grade non-Hodgkin’s lymphoma. Oncologist 9:160–72.

    Article  CAS  Google Scholar 

  27. Grossbard ML, Multani PS, Freedman AS et al. (1999) A Phase II study of adjuvant therapy with anti-B4-blocked ricin after autologous bone marrow transplantation for patients with relapsed B-cell non-Hodgkin’s lymphoma. Clin. Cancer Res. 5:2392–8.

    CAS  PubMed  Google Scholar 

  28. Coleman M, Goldenberg DM, Siegel AB et al. (2003) Epratuzumab: targeting B-cell malignancies through CD22. Clin. Cancer Res. 9:3991–4S.

    Google Scholar 

  29. Keating M, Coutre S, Rai K et al. (2004) Management guidelines for use of alemtuzumab in B-cell chronic lymphocytic leukemia. Clin. Lymphoma 4:220–7.

    Article  CAS  Google Scholar 

  30. Wiland AM and Philosophe B. (2004) Daclizumab induction in solid organ transplantation. Expert Opin. Biol. Ther. 4:729–40.

    Article  CAS  Google Scholar 

  31. Chapman TM, Keating GM. (2003) Basiliximab: a review of its use as induction therapy in renal transplantation. Drugs 63:2803–35.

    Article  CAS  Google Scholar 

  32. Lo-Coco F, Cimino G, Breccia M et al. (2004) Gentuzumab ozogamicin (“mylotarg”) as a single agent for molecularly relapsed acute promyelocytic leukemia. Blood 104:1995–9.

    Article  CAS  Google Scholar 

  33. Ball ED, Selvaggi K, Hurd D et al. (1995) Phase I clinical trial of serotherapy in patients with acute myeloid leukemia with an immunoglobulin M monoclonal antibody to CD15. Clin. Cancer Res. 1:965–72.

    CAS  PubMed  Google Scholar 

  34. Pegram MD, Pienkowski T, Northfelt DW, et al. (2004) Results of two open-label, multicenter phase II studies of docetaxel, platinum salts, and trastuzumab in HER2-positive advanced breast cancer. J. Natl. Cancer Inst. 19:759–69.

    Article  Google Scholar 

  35. Nahta R, Hung MC, Esteva FJ. (2004) The HER-2-targeting antibodies trastuzumab and pertuzumab synergistically inhibit the survival of breast cancer cells. Cancer Res. 64:2343–6.

    Article  CAS  Google Scholar 

  36. Richman CM, DeNardo SJ. (2001) Systemic radiotherapy in metastatic breast cancer using 90Y-linked monoclonal MUC-1 antibodies. Crit. Rev. Oncol. Hematol. 38:25–35.

    Article  CAS  Google Scholar 

  37. Brooks D, Taylor C, Dos SB et al. (1995) Phase Ia trial of murine immunoglobulin A antitransferrin receptor antibody 42/6. Clin. Cancer Res. 1:1259–65.

    CAS  PubMed  Google Scholar 

  38. Blumenthal RD. (2004) Technology evaluation: cT84.66, City of Hope. Curr. Opin. Mol. Ther. 6:90–5.

    CAS  PubMed  Google Scholar 

  39. Chatenoud L, Bach JF. (1993) Therapeutic monoclonal antibodies in transplantation. Transplant. Proc. 25:473–4.

    CAS  PubMed  Google Scholar 

  40. Gottlieb A, Lebwohl M, Shirin S et al. (2000) Anti-CD4 monoclonal antibody treatment of moderate to severe psoriasis vulgaris: Results of a pilot, multicenter, multiple-dose, placebo-controlled study. Amer. Acad. of Dermatol. 43:595–604.

    Article  CAS  Google Scholar 

  41. Dubertret L, Sterry W, Bos JD et al. (2006) Clinical experience acquired with the efalizumab (Raptiva) (CLEAR) trial in patients with moderate-to-severe plaque psoriasis: results from a phase III international randomized, placebo-controlled trial. Brit. J. Dermatol. 155:170–81.

    Article  CAS  Google Scholar 

  42. Edwards JCW, Szczepanski L, Szechinski J et al. (2004) Efficacy of B-cell-targeted therapy with Rituximab in patients with rheumatoid arthritis. New England J. Med. 350:2572–81.

    Article  CAS  Google Scholar 

  43. Waldmann TA, O’Shea J. (1998) The use of antibodies against the IL-2 receptor in transplantation. Curr. Opin. Immunol. 10:507–12.

    Article  CAS  Google Scholar 

  44. Dick AD, Meyer P, James T, Forrester JV, Hale G, Waldmann H, Isaacs JD. (2000) Campath-1H therapy in refractory ocular inflammatory disease. Br. J. Ophthalmol. 84:107–9.

    Article  CAS  Google Scholar 

  45. Kuwana M, Nomura S, Fujimura K et al. (2004) Effect of a single injection of humanized anti-CD154 monoclonal antibody on the platelet-specific autoimmune response in patients with immune thrombocytopenic purpura. Blood 103:1229–36.

    Article  CAS  Google Scholar 

  46. Brekke OH, Sandlie I. (2003). Therapeutic antibodies for human disease at the dawn of the twenty-first century. Nature Reviews Drug Discovery. 2:52–62.

    Article  CAS  Google Scholar 

  47. Teeling JL, French RR, Cragg MS et al. (2004) Characterization of new human CD20 monoclonal antibodies with potent cytolytic activity against non-Hodgkin lymphomas. Blood 104:1793–800.

    Article  CAS  Google Scholar 

  48. Glennie MJ, Johnson PWM. (2000) Clinical trials of antibody therapy. Immunol. Today. 21:403–10.

    Article  CAS  Google Scholar 

  49. Pastan I, Hassan R, Fitzgerald DJ, Kreitman RJ. (2006) Immunotoxin therapy of cancer. Nature Reviews Cancer. 6:559–65.

    Article  CAS  Google Scholar 

  50. Cardarelli RM, Quinn M, Buckman D et al. (2002) Binding to CD20 by Anti-B1 Antibody of F(ab′)2 is sufficient for induction of apoptosis in B-cell lines. Cancer Immunol. Immunother. 51:15–24

    Article  CAS  Google Scholar 

  51. Teeling JL, Mackus WJM, Wiegman LJJM et al. (2006) The Biological Activity of Human CD20 Monoclonal Antibodies is linked to unique Epitopes on CD201. J. of Immunol. 177:362–71.

    Article  CAS  Google Scholar 

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Acknowledgments

The Author’s studies in the area of leukocyte cell surface molecules have been supported by the Australian National Health and Medical Research Council, by the Co-operative Research Centre for Diagnostics, and by the Human Leukocyte Differentiation Antigens Workshops. I thank Dr Alice Beare and Ms Silvia Nobbs for Figure 1.

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  1. Child Health Research Institute, Women’s and Children’s Hospital, Adelaide, and Co-operative Research Centre for Diagnostics, 72 King William Road, North Adelaide, SA5006, Australia

    Heddy Zola

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Correspondence to Heddy Zola.

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Zola, H. Medical Applications of Leukocyte Surface Molecules—the CD molecules. Mol Med 12, 312–316 (2006). https://doi.org/10.2119/2006-00081.Zola

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