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Erschienen in: Inflammation Research 7/2017

10.03.2017 | Review

The immunological function of CD52 and its targeting in organ transplantation

verfasst von: Yang Zhao, Huiting Su, Xiaofei Shen, Junfeng Du, Xiaodong Zhang, Yong Zhao

Erschienen in: Inflammation Research | Ausgabe 7/2017

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Abstract

Introduction

CD52 (Campath-1 antigen), a glycoprotein of 12 amino acids anchored to glycosylphosphatidylinositol, is widely expressed on the cell surface of immune cells, such as mature lymphocytes, natural killer cells (NK), eosinophils, neutrophils, monocytes/macrophages, and dendritic cells (DCs). The anti-CD52 mAb, alemtuzumab, was used widely in clinics for the treatment of patients such as organ transplantation. In the present manuscript, we will briefly summarize the immunological function of CD52 and discuss the application of anti-CD52 mAb in transplantation settings.

Findings

We reviewed studies published until July 2016 to explore the role of CD52 in immune cell function and its implication in organ transplantation. We showed that ligation of cell surface CD52 molecules may offer costimulatory signals for T-cell activation and proliferation. However, soluble CD52 molecules will interact with the inhibitory sialic acid-binding immunoglobulin-like lectin 10 (Siglec10) to significantly inhibit T cell proliferation and activation. Although the physiological and pathological significances of CD52 molecules are still poorly understood, the anti-CD52 mAb, alemtuzumab, was used widely for the treatment of patients with chronic lymphocytic leukemia, autoimmune diseases as well as cell and organ transplantation in clinics.

Conclusion

Studies clearly showed that CD52 can modulate T-cell activation either by its intracellular signal pathways or by the interaction of soluble CD52 and Siglec-10 expressing on T cells. However, the regulatory functions of CD52 on other immune cell subpopulations in organ transplantation require to be studied in the near future.
Literatur
2.
Zurück zum Zitat Xia MQ, et al. Structure of the CAMPATH-1 antigen, a glycosylphosphatidylinositol-anchored glycoprotein which is an exceptionally good target for complement lysis. Biochem J. 1993;293(Pt 3):633–40.PubMedPubMedCentralCrossRef Xia MQ, et al. Structure of the CAMPATH-1 antigen, a glycosylphosphatidylinositol-anchored glycoprotein which is an exceptionally good target for complement lysis. Biochem J. 1993;293(Pt 3):633–40.PubMedPubMedCentralCrossRef
3.
Zurück zum Zitat Cheetham GM, et al. Crystal structures of a rat anti-CD52 (CAMPATH-1) therapeutic antibody Fab fragment and its humanized counterpart. J Mol Biol. 1998;284(1):85–99.PubMedCrossRef Cheetham GM, et al. Crystal structures of a rat anti-CD52 (CAMPATH-1) therapeutic antibody Fab fragment and its humanized counterpart. J Mol Biol. 1998;284(1):85–99.PubMedCrossRef
4.
Zurück zum Zitat Kirchhoff C, et al. A major mRNA of the human epididymal principal cells, HE5, encodes the leucocyte differentiation CDw52 antigen peptide backbone. Mol Reprod Dev. 1993;34(1):8–15.PubMedCrossRef Kirchhoff C, et al. A major mRNA of the human epididymal principal cells, HE5, encodes the leucocyte differentiation CDw52 antigen peptide backbone. Mol Reprod Dev. 1993;34(1):8–15.PubMedCrossRef
5.
Zurück zum Zitat Buggins AG, et al. Peripheral blood but not tissue dendritic cells express CD52 and are depleted by treatment with alemtuzumab. Blood. 2002;100(5):1715–20.PubMed Buggins AG, et al. Peripheral blood but not tissue dendritic cells express CD52 and are depleted by treatment with alemtuzumab. Blood. 2002;100(5):1715–20.PubMed
6.
Zurück zum Zitat Ratzinger G, et al. Differential CD52 expression by distinct myeloid dendritic cell subsets: implications for alemtuzumab activity at the level of antigen presentation in allogeneic graft-host interactions in transplantation. Blood. 2003;101(4):1422–9.PubMedCrossRef Ratzinger G, et al. Differential CD52 expression by distinct myeloid dendritic cell subsets: implications for alemtuzumab activity at the level of antigen presentation in allogeneic graft-host interactions in transplantation. Blood. 2003;101(4):1422–9.PubMedCrossRef
7.
Zurück zum Zitat Hale G. The CD52 antigen and development of the CAMPATH antibodies. CytoTherapy. 2001;3(3):137–43.PubMedCrossRef Hale G. The CD52 antigen and development of the CAMPATH antibodies. CytoTherapy. 2001;3(3):137–43.PubMedCrossRef
8.
9.
Zurück zum Zitat Cohen JA, et al. Alemtuzumab versus interferon beta 1a as first-line treatment for patients with relapsing-remitting multiple sclerosis: a randomised controlled phase 3 trial. Lancet. 2012;380(9856):1819–28.PubMedCrossRef Cohen JA, et al. Alemtuzumab versus interferon beta 1a as first-line treatment for patients with relapsing-remitting multiple sclerosis: a randomised controlled phase 3 trial. Lancet. 2012;380(9856):1819–28.PubMedCrossRef
10.
Zurück zum Zitat Garnock-Jones KP. Alemtuzumab: a review of its use in patients with relapsing multiple sclerosis. Drugs. 2014;74(4):489–504.PubMedCrossRef Garnock-Jones KP. Alemtuzumab: a review of its use in patients with relapsing multiple sclerosis. Drugs. 2014;74(4):489–504.PubMedCrossRef
11.
Zurück zum Zitat Fox EJ, et al. Alemtuzumab improves neurological functional systems in treatment-naive relapsing-remitting multiple sclerosis patients. J Neurol Sci. 2016;363:188–94.PubMedCrossRef Fox EJ, et al. Alemtuzumab improves neurological functional systems in treatment-naive relapsing-remitting multiple sclerosis patients. J Neurol Sci. 2016;363:188–94.PubMedCrossRef
12.
Zurück zum Zitat Hui YM, et al. Use of non-irradiated blood components in Campath (alemtuzumab)-treated renal transplant patients. Transfus Med. 2016;26(2):138–46.PubMedCrossRef Hui YM, et al. Use of non-irradiated blood components in Campath (alemtuzumab)-treated renal transplant patients. Transfus Med. 2016;26(2):138–46.PubMedCrossRef
13.
Zurück zum Zitat Schub N, et al. Therapy of steroid-refractory acute GVHD with CD52 antibody alemtuzumab is effective. Bone Marrow Transplant. 2011;46(1):143–7.PubMedCrossRef Schub N, et al. Therapy of steroid-refractory acute GVHD with CD52 antibody alemtuzumab is effective. Bone Marrow Transplant. 2011;46(1):143–7.PubMedCrossRef
14.
Zurück zum Zitat Li SW, et al. All-trans-retinoic acid induces CD52 expression in acute promyelocytic leukemia. Blood. 2003;101(5):1977–80.PubMedCrossRef Li SW, et al. All-trans-retinoic acid induces CD52 expression in acute promyelocytic leukemia. Blood. 2003;101(5):1977–80.PubMedCrossRef
15.
Zurück zum Zitat Gilleece MH, Dexter TM. Effect of Campath-1H antibody on human hematopoietic progenitors in vitro. Blood. 1993;82(3):807–12.PubMed Gilleece MH, Dexter TM. Effect of Campath-1H antibody on human hematopoietic progenitors in vitro. Blood. 1993;82(3):807–12.PubMed
16.
Zurück zum Zitat Elsner J, et al. Surface and mRNA expression of the CD52 antigen by human eosinophils but not by neutrophils. Blood. 1996;88(12):4684–93.PubMed Elsner J, et al. Surface and mRNA expression of the CD52 antigen by human eosinophils but not by neutrophils. Blood. 1996;88(12):4684–93.PubMed
17.
Zurück zum Zitat Knechtle SJ, et al. Campath-1H in renal transplantation: The University of Wisconsin experience. Surgery. 2004;136(4):754–60.PubMedCrossRef Knechtle SJ, et al. Campath-1H in renal transplantation: The University of Wisconsin experience. Surgery. 2004;136(4):754–60.PubMedCrossRef
18.
Zurück zum Zitat Ambrose LR, Morel AS, Warrens AN. Neutrophils express CD52 and exhibit complement-mediated lysis in the presence of alemtuzumab. Blood. 2009;114(14):3052–5.PubMedCrossRef Ambrose LR, Morel AS, Warrens AN. Neutrophils express CD52 and exhibit complement-mediated lysis in the presence of alemtuzumab. Blood. 2009;114(14):3052–5.PubMedCrossRef
19.
20.
Zurück zum Zitat Olweus J, Lund-Johansen F, Terstappen LW. Expression of cell surface markers during differentiation of CD34+, CD38-/lo fetal and adult bone marrow cells. Immunomethods. 1994;5(3):179–88.PubMedCrossRef Olweus J, Lund-Johansen F, Terstappen LW. Expression of cell surface markers during differentiation of CD34+, CD38-/lo fetal and adult bone marrow cells. Immunomethods. 1994;5(3):179–88.PubMedCrossRef
21.
Zurück zum Zitat Williams RJ, et al. Impact on T-cell depletion and CD34+ cell recovery using humanised CD52 monoclonal antibody (CAMPATH-1H) in BM and PSBC collections; comparison with CAMPATH-1M and CAMPATH-1G. CytoTherapy. 2000;2(1):5–14.PubMedCrossRef Williams RJ, et al. Impact on T-cell depletion and CD34+ cell recovery using humanised CD52 monoclonal antibody (CAMPATH-1H) in BM and PSBC collections; comparison with CAMPATH-1M and CAMPATH-1G. CytoTherapy. 2000;2(1):5–14.PubMedCrossRef
22.
Zurück zum Zitat Xia MQ, et al. Characterization of the CAMPATH-1 (CDw52) antigen: biochemical analysis and cDNA cloning reveal an unusually small peptide backbone. Eur J Immunol. 1991;21(7):1677–84.PubMedCrossRef Xia MQ, et al. Characterization of the CAMPATH-1 (CDw52) antigen: biochemical analysis and cDNA cloning reveal an unusually small peptide backbone. Eur J Immunol. 1991;21(7):1677–84.PubMedCrossRef
23.
Zurück zum Zitat Bandala-Sanchez E, et al. T cell regulation mediated by interaction of soluble CD52 with the inhibitory receptor Siglec-10. Nat Immunol. 2013;14(7):741–8.PubMedCrossRef Bandala-Sanchez E, et al. T cell regulation mediated by interaction of soluble CD52 with the inhibitory receptor Siglec-10. Nat Immunol. 2013;14(7):741–8.PubMedCrossRef
24.
Zurück zum Zitat Rowan W, et al. Cross-linking of the CAMPATH-1 antigen (CD52) mediates growth inhibition in human B- and T-lymphoma cell lines, and subsequent emergence of CD52-deficient cells. Immunology. 1998;95(3):427–36.PubMedPubMedCentralCrossRef Rowan W, et al. Cross-linking of the CAMPATH-1 antigen (CD52) mediates growth inhibition in human B- and T-lymphoma cell lines, and subsequent emergence of CD52-deficient cells. Immunology. 1998;95(3):427–36.PubMedPubMedCentralCrossRef
25.
Zurück zum Zitat Nuckel H, et al. Alemtuzumab induces enhanced apoptosis in vitro in B-cells from patients with chronic lymphocytic leukemia by antibody-dependent cellular cytotoxicity. Eur J Pharmacol. 2005;514(2–3):217–24.PubMedCrossRef Nuckel H, et al. Alemtuzumab induces enhanced apoptosis in vitro in B-cells from patients with chronic lymphocytic leukemia by antibody-dependent cellular cytotoxicity. Eur J Pharmacol. 2005;514(2–3):217–24.PubMedCrossRef
26.
Zurück zum Zitat Mone AP, et al. Alemtuzumab induces caspase-independent cell death in human chronic lymphocytic leukemia cells through a lipid raft-dependent mechanism. Leukemia. 2006;20(2):272–9.PubMedCrossRef Mone AP, et al. Alemtuzumab induces caspase-independent cell death in human chronic lymphocytic leukemia cells through a lipid raft-dependent mechanism. Leukemia. 2006;20(2):272–9.PubMedCrossRef
27.
Zurück zum Zitat Smolewski P, et al. Additive cytotoxic effect of bortezomib in combination with anti-CD20 or anti-CD52 monoclonal antibodies on chronic lymphocytic leukemia cells. Leuk Res. 2006;30(12):1521–9.PubMedCrossRef Smolewski P, et al. Additive cytotoxic effect of bortezomib in combination with anti-CD20 or anti-CD52 monoclonal antibodies on chronic lymphocytic leukemia cells. Leuk Res. 2006;30(12):1521–9.PubMedCrossRef
28.
Zurück zum Zitat Nguyen TH, et al. Alemtuzumab induction of intracellular signaling and apoptosis in malignant B lymphocytes. Leuk Lymphoma. 2012;53(4):699–709.PubMedCrossRef Nguyen TH, et al. Alemtuzumab induction of intracellular signaling and apoptosis in malignant B lymphocytes. Leuk Lymphoma. 2012;53(4):699–709.PubMedCrossRef
29.
Zurück zum Zitat Rowan WC, et al. Cross-linking of the CAMPATH-1 antigen (CD52) triggers activation of normal human T lymphocytes. Int Immunol. 1995;7(1):69–77.PubMedCrossRef Rowan WC, et al. Cross-linking of the CAMPATH-1 antigen (CD52) triggers activation of normal human T lymphocytes. Int Immunol. 1995;7(1):69–77.PubMedCrossRef
30.
Zurück zum Zitat Hederer RA, et al. The CD45 tyrosine phosphatase regulates Campath-1H (CD52)-induced TCR-dependent signal transduction in human T cells. Int Immunol. 2000;12(4):505–16.PubMedCrossRef Hederer RA, et al. The CD45 tyrosine phosphatase regulates Campath-1H (CD52)-induced TCR-dependent signal transduction in human T cells. Int Immunol. 2000;12(4):505–16.PubMedCrossRef
31.
Zurück zum Zitat Masuyama J, et al. A novel costimulation pathway via the 4C8 antigen for the induction of CD4 + regulatory T cells. J Immunol. 2002;169(7):3710–6.PubMedCrossRef Masuyama J, et al. A novel costimulation pathway via the 4C8 antigen for the induction of CD4 + regulatory T cells. J Immunol. 2002;169(7):3710–6.PubMedCrossRef
32.
Zurück zum Zitat Masuyama J, et al. Characterization of the 4C8 antigen involved in transendothelial migration of CD26(hi) T cells after tight adhesion to human umbilical vein endothelial cell monolayers. J Exp Med. 1999;189(6):979–90.PubMedPubMedCentralCrossRef Masuyama J, et al. Characterization of the 4C8 antigen involved in transendothelial migration of CD26(hi) T cells after tight adhesion to human umbilical vein endothelial cell monolayers. J Exp Med. 1999;189(6):979–90.PubMedPubMedCentralCrossRef
33.
Zurück zum Zitat Watanabe T, et al. CD52 is a novel costimulatory molecule for induction of CD4+ regulatory T cells. Clin Immunol. 2006;120(3):247–59.PubMedCrossRef Watanabe T, et al. CD52 is a novel costimulatory molecule for induction of CD4+ regulatory T cells. Clin Immunol. 2006;120(3):247–59.PubMedCrossRef
34.
Zurück zum Zitat Pant AB, et al. Alteration of CD39+ Foxp3+ CD4 T cell and cytokine levels in EAE/MS following anti-CD52 treatment. J Neuroimmunol. 2017;303:22–30.PubMedCrossRef Pant AB, et al. Alteration of CD39+ Foxp3+ CD4 T cell and cytokine levels in EAE/MS following anti-CD52 treatment. J Neuroimmunol. 2017;303:22–30.PubMedCrossRef
35.
Zurück zum Zitat Shah A, et al. CD52 ligation induces CD4 and CD8 down modulation in vivo and in vitro. Transpl Int. 2006;19(9):749–58.PubMedCrossRef Shah A, et al. CD52 ligation induces CD4 and CD8 down modulation in vivo and in vitro. Transpl Int. 2006;19(9):749–58.PubMedCrossRef
36.
37.
38.
Zurück zum Zitat Lowenstein H, et al. Different mechanisms of Campath-1H-mediated depletion for CD4 and CD8 T cells in peripheral blood. Transpl Int. 2006;19(11):927–36.PubMedCrossRef Lowenstein H, et al. Different mechanisms of Campath-1H-mediated depletion for CD4 and CD8 T cells in peripheral blood. Transpl Int. 2006;19(11):927–36.PubMedCrossRef
39.
Zurück zum Zitat Stauch D, et al. Targeting of natural killer cells by rabbit antithymocyte globulin and campath-1H: similar effects independent of specificity. PLoS One. 2009;4(3):e4709.PubMedPubMedCentralCrossRef Stauch D, et al. Targeting of natural killer cells by rabbit antithymocyte globulin and campath-1H: similar effects independent of specificity. PLoS One. 2009;4(3):e4709.PubMedPubMedCentralCrossRef
40.
Zurück zum Zitat Shen B, et al. Impact of antimouse CD52 monoclonal antibody on Graft’s gamma delta intraepithelial lymphocytes after orthotopic small bowel transplantation in Mice. Transplantation. 2013;95(5):663–70.PubMedCrossRef Shen B, et al. Impact of antimouse CD52 monoclonal antibody on Graft’s gamma delta intraepithelial lymphocytes after orthotopic small bowel transplantation in Mice. Transplantation. 2013;95(5):663–70.PubMedCrossRef
41.
Zurück zum Zitat Rodig SJ, et al. Heterogeneous CD52 expression among hematologic neoplasms: implications for the use of alemtuzumab (CAMPATH-1H). Clin Cancer Res. 2006;12(23):7174–9.PubMedCrossRef Rodig SJ, et al. Heterogeneous CD52 expression among hematologic neoplasms: implications for the use of alemtuzumab (CAMPATH-1H). Clin Cancer Res. 2006;12(23):7174–9.PubMedCrossRef
42.
Zurück zum Zitat Dearden CE, Matutes E. Alemtuzumab in T-cell lymphoproliferative disorders. Best Practice Research Clinical Haematology. 2006;19(4):795–810.PubMedCrossRef Dearden CE, Matutes E. Alemtuzumab in T-cell lymphoproliferative disorders. Best Practice Research Clinical Haematology. 2006;19(4):795–810.PubMedCrossRef
43.
Zurück zum Zitat Cabrera R, et al. Using an immune functional assay to differentiate acute cellular rejection from recurrent hepatitis c in liver transplant patients. Liver Transplant. 2009;15(2):216–22.CrossRef Cabrera R, et al. Using an immune functional assay to differentiate acute cellular rejection from recurrent hepatitis c in liver transplant patients. Liver Transplant. 2009;15(2):216–22.CrossRef
44.
Zurück zum Zitat Magliocca JF, Knechtle SJ. The evolving role of alemtuzumab (Campath-1H) for immunosuppressive therapy in organ transplantation. Transplant Int. 2006;19(9):705–14.CrossRef Magliocca JF, Knechtle SJ. The evolving role of alemtuzumab (Campath-1H) for immunosuppressive therapy in organ transplantation. Transplant Int. 2006;19(9):705–14.CrossRef
45.
46.
Zurück zum Zitat Zhang X, et al. Differential reconstitution of T cell subsets following immunodepleting treatment with alemtuzumab (Anti-CD52 Monoclonal Antibody) in patients with relapsing-remitting multiple sclerosis. J Immunol. 2013;191(12):5867–74.PubMedCrossRef Zhang X, et al. Differential reconstitution of T cell subsets following immunodepleting treatment with alemtuzumab (Anti-CD52 Monoclonal Antibody) in patients with relapsing-remitting multiple sclerosis. J Immunol. 2013;191(12):5867–74.PubMedCrossRef
47.
Zurück zum Zitat Jones JL, et al. Improvement in disability after alemtuzumab treatment of multiple sclerosis is associated with neuroprotective autoimmunity. Brain. 2010;133:2232–47.PubMedCrossRef Jones JL, et al. Improvement in disability after alemtuzumab treatment of multiple sclerosis is associated with neuroprotective autoimmunity. Brain. 2010;133:2232–47.PubMedCrossRef
48.
Zurück zum Zitat Chakraverty R, et al. Limiting transplantation-related mortality following unrelated donor stem cell transplantation by using a nonmyeloablative conditioning regimen. Blood. 2002;99(3):1071–8.PubMedCrossRef Chakraverty R, et al. Limiting transplantation-related mortality following unrelated donor stem cell transplantation by using a nonmyeloablative conditioning regimen. Blood. 2002;99(3):1071–8.PubMedCrossRef
49.
Zurück zum Zitat Kottaridis PD, et al. In vivo CAMPATH-1H prevents graft-versus-host disease following nonmyeloablative stem cell transplantation. Blood. 2000;96(7):2419–25.PubMed Kottaridis PD, et al. In vivo CAMPATH-1H prevents graft-versus-host disease following nonmyeloablative stem cell transplantation. Blood. 2000;96(7):2419–25.PubMed
50.
Zurück zum Zitat Kirsch BM, et al. Alemtuzumab (Campath-1H) induction therapy and dendritic cells: Impact on peripheral dendritic cell repertoire in renal allograft recipients. Transpl Immunol. 2006;16(3–4):254–7.PubMedCrossRef Kirsch BM, et al. Alemtuzumab (Campath-1H) induction therapy and dendritic cells: Impact on peripheral dendritic cell repertoire in renal allograft recipients. Transpl Immunol. 2006;16(3–4):254–7.PubMedCrossRef
51.
Zurück zum Zitat Klangsinsirikul P, et al. Campath-1G causes rapid depletion of circulating host dendritic cells (DCs) before allogeneic transplantation but does not delay donor DC reconstitution. Blood. 2002;99(7):2586–91.PubMedCrossRef Klangsinsirikul P, et al. Campath-1G causes rapid depletion of circulating host dendritic cells (DCs) before allogeneic transplantation but does not delay donor DC reconstitution. Blood. 2002;99(7):2586–91.PubMedCrossRef
52.
Zurück zum Zitat Siders WM, et al. Involvement of neutrophils and natural killer cells in the anti-tumor activity of alemtuzumab in xenograft tumor models. Leuk Lymphoma. 2010;51(7):1293–304.PubMedCrossRef Siders WM, et al. Involvement of neutrophils and natural killer cells in the anti-tumor activity of alemtuzumab in xenograft tumor models. Leuk Lymphoma. 2010;51(7):1293–304.PubMedCrossRef
53.
Zurück zum Zitat Gorin NC, et al. Administration of alemtuzumab and G-CSF to adults with relapsed or refractory acute lymphoblastic leukemia: results of a phase II study. Eur J Haematol. 2013;91(4):315–21.PubMed Gorin NC, et al. Administration of alemtuzumab and G-CSF to adults with relapsed or refractory acute lymphoblastic leukemia: results of a phase II study. Eur J Haematol. 2013;91(4):315–21.PubMed
54.
Zurück zum Zitat Neerukonda AR, et al. refractory adult primary autoimmune neutropenia that responded to Alemtuzumab. Intern Med. 2016;55(12):1667–70.PubMedCrossRef Neerukonda AR, et al. refractory adult primary autoimmune neutropenia that responded to Alemtuzumab. Intern Med. 2016;55(12):1667–70.PubMedCrossRef
55.
Zurück zum Zitat Masuyama J, et al. Ex vivo expansion of natural killer cells from human peripheral blood mononuclear cells co-stimulated with anti-CD3 and anti-CD52 monoclonal antibodies. CytoTherapy. 2016;18(1):80–90.PubMedCrossRef Masuyama J, et al. Ex vivo expansion of natural killer cells from human peripheral blood mononuclear cells co-stimulated with anti-CD3 and anti-CD52 monoclonal antibodies. CytoTherapy. 2016;18(1):80–90.PubMedCrossRef
56.
Zurück zum Zitat Naparstek E, et al. Engraftment of marrow allografts treated with Campath-1 monoclonal antibodies. Exp Hematol. 1999;27(7):1210–8.PubMedCrossRef Naparstek E, et al. Engraftment of marrow allografts treated with Campath-1 monoclonal antibodies. Exp Hematol. 1999;27(7):1210–8.PubMedCrossRef
57.
Zurück zum Zitat Dyer MJ, et al. Effects of CAMPATH-1 antibodies in vivo in patients with lymphoid malignancies: influence of antibody isotype. Blood. 1989;73(6):1431–9.PubMed Dyer MJ, et al. Effects of CAMPATH-1 antibodies in vivo in patients with lymphoid malignancies: influence of antibody isotype. Blood. 1989;73(6):1431–9.PubMed
58.
Zurück zum Zitat Hale G, et al. Remission induction in non-Hodgkin lymphoma with reshaped human monoclonal antibody CAMPATH-1H. The Lancet. 1988;2(8625):1394–9.CrossRef Hale G, et al. Remission induction in non-Hodgkin lymphoma with reshaped human monoclonal antibody CAMPATH-1H. The Lancet. 1988;2(8625):1394–9.CrossRef
59.
Zurück zum Zitat Ciancio G, et al. The use of campath-1H as induction therapy in renal transplantation: Preliminary results. Transplantation. 2004;78(3):426–33.PubMedCrossRef Ciancio G, et al. The use of campath-1H as induction therapy in renal transplantation: Preliminary results. Transplantation. 2004;78(3):426–33.PubMedCrossRef
60.
Zurück zum Zitat Kirk AD, et al. Results from a human renal allograft tolerance trial evaluating the humanized CD52-specific monoclonal antibody alemtuzumab (Campath-1H). Transplantation. 2003;76(1):120–9.PubMedCrossRef Kirk AD, et al. Results from a human renal allograft tolerance trial evaluating the humanized CD52-specific monoclonal antibody alemtuzumab (Campath-1H). Transplantation. 2003;76(1):120–9.PubMedCrossRef
61.
Zurück zum Zitat Bloom DD, et al. T-lymphocyte alloresponses of Campath-1H-treated kidney transplant patients. Transplantation. 2006;81(1):81–7.PubMedCrossRef Bloom DD, et al. T-lymphocyte alloresponses of Campath-1H-treated kidney transplant patients. Transplantation. 2006;81(1):81–7.PubMedCrossRef
62.
Zurück zum Zitat Knechtle SJ, et al. Campath-1H induction plus rapamycin monotherapy for renal transplantation: results of a pilot study. Am J Transplant. 2003;3(6):722–30.PubMedCrossRef Knechtle SJ, et al. Campath-1H induction plus rapamycin monotherapy for renal transplantation: results of a pilot study. Am J Transplant. 2003;3(6):722–30.PubMedCrossRef
63.
Zurück zum Zitat Shapiro, R., et al. Kidney transplantation under minimal immunosuppression after pretransplant lymphoid depletion with Thymoglobulin or Campath. J Am Coll Surg, 2005;200(4): 505–15; quiz A59–61.CrossRef Shapiro, R., et al. Kidney transplantation under minimal immunosuppression after pretransplant lymphoid depletion with Thymoglobulin or Campath. J Am Coll Surg, 2005;200(4): 505–15; quiz A59–61.CrossRef
64.
Zurück zum Zitat Hale G, et al. Improving the outcome of bone marrow transplantation by using CD52 monoclonal antibodies to prevent graft-versus-host disease and graft rejection. Blood. 1998;92(12):4581–90.PubMed Hale G, et al. Improving the outcome of bone marrow transplantation by using CD52 monoclonal antibodies to prevent graft-versus-host disease and graft rejection. Blood. 1998;92(12):4581–90.PubMed
65.
Zurück zum Zitat Hale G, et al. CD52 antibodies for prevention of graft-versus-host disease and graft rejection following transplantation of allogeneic peripheral blood stem cells. Bone Marrow Transplant. 2000;26(1):69–76.PubMedCrossRef Hale G, et al. CD52 antibodies for prevention of graft-versus-host disease and graft rejection following transplantation of allogeneic peripheral blood stem cells. Bone Marrow Transplant. 2000;26(1):69–76.PubMedCrossRef
66.
Zurück zum Zitat Hale G, et al. Pilot study of CAMPATH-1, a rat monoclonal antibody that fixes human complement, as an immunosuppressant in organ transplantation. Transplantation. 1986;42(3):308–11.PubMedCrossRef Hale G, et al. Pilot study of CAMPATH-1, a rat monoclonal antibody that fixes human complement, as an immunosuppressant in organ transplantation. Transplantation. 1986;42(3):308–11.PubMedCrossRef
67.
Zurück zum Zitat Friend PJ, et al. Campath-1M–prophylactic use after kidney transplantation. A randomized controlled clinical trial. Transplantation. 1989;48(2):248–53.PubMedCrossRef Friend PJ, et al. Campath-1M–prophylactic use after kidney transplantation. A randomized controlled clinical trial. Transplantation. 1989;48(2):248–53.PubMedCrossRef
68.
Zurück zum Zitat Friend PJ, et al. Reversal of allograft rejection using the monoclonal antibody, Campath-1G. Transplant Proc. 1991;23(4):2253–4.PubMed Friend PJ, et al. Reversal of allograft rejection using the monoclonal antibody, Campath-1G. Transplant Proc. 1991;23(4):2253–4.PubMed
69.
Zurück zum Zitat Isaacs JD, et al. CAMPATH-1H in rheumatoid arthritis–an intravenous dose-ranging study. Br J Rheumatol. 1996;35(3):231–40.PubMedCrossRef Isaacs JD, et al. CAMPATH-1H in rheumatoid arthritis–an intravenous dose-ranging study. Br J Rheumatol. 1996;35(3):231–40.PubMedCrossRef
71.
Zurück zum Zitat Cheung WW, et al. Alemtuzumab induced complete remission of autoimmune hemolytic anemia refractory to corticosteroids, splenectomy and rituximab. Haematologica. 2006;91(5 Suppl):ECR13.PubMed Cheung WW, et al. Alemtuzumab induced complete remission of autoimmune hemolytic anemia refractory to corticosteroids, splenectomy and rituximab. Haematologica. 2006;91(5 Suppl):ECR13.PubMed
72.
Zurück zum Zitat Morales J, et al. Alemtuzumab induction in kidney transplantation: clinical results and impact on T-regulatory cells. Transplant Proc. 2008;40(9):3223–8.PubMedCrossRef Morales J, et al. Alemtuzumab induction in kidney transplantation: clinical results and impact on T-regulatory cells. Transplant Proc. 2008;40(9):3223–8.PubMedCrossRef
73.
Zurück zum Zitat Watson CJ, et al. Alemtuzumab (CAMPATH 1 H) induction therapy in cadaveric kidney transplantation–efficacy and safety at five years. Am J Transplant. 2005;5(6):1347–53.PubMedCrossRef Watson CJ, et al. Alemtuzumab (CAMPATH 1 H) induction therapy in cadaveric kidney transplantation–efficacy and safety at five years. Am J Transplant. 2005;5(6):1347–53.PubMedCrossRef
74.
Zurück zum Zitat Coles AJ, et al. Alemtuzumab vs. interferon beta-1a in early multiple sclerosis. N Engl J Med. 2008;359(17):1786–801.PubMedCrossRef Coles AJ, et al. Alemtuzumab vs. interferon beta-1a in early multiple sclerosis. N Engl J Med. 2008;359(17):1786–801.PubMedCrossRef
75.
Zurück zum Zitat Bartosh SM, Knechtle SJ, Sollinger HW. Campath-1H use in pediatric renal transplantation. Am J Transplant. 2005;5(6):1569–73.PubMedCrossRef Bartosh SM, Knechtle SJ, Sollinger HW. Campath-1H use in pediatric renal transplantation. Am J Transplant. 2005;5(6):1569–73.PubMedCrossRef
76.
Zurück zum Zitat Nankivell BJ, et al. The natural history of chronic allograft nephropathy. N Engl J Med. 2003;349(24):2326–33.PubMedCrossRef Nankivell BJ, et al. The natural history of chronic allograft nephropathy. N Engl J Med. 2003;349(24):2326–33.PubMedCrossRef
77.
Zurück zum Zitat Viklicky O, et al. Sequential targeting of CD52 and TNF allows early minimization therapy in kidney transplantation: from a biomarker to targeting in a proof-of-concept trial. PLoS One. 2017;12(1):e0169624.PubMedPubMedCentralCrossRef Viklicky O, et al. Sequential targeting of CD52 and TNF allows early minimization therapy in kidney transplantation: from a biomarker to targeting in a proof-of-concept trial. PLoS One. 2017;12(1):e0169624.PubMedPubMedCentralCrossRef
78.
Zurück zum Zitat Meier-Kriesche HU, Schold JD, Kaplan B. Long-term renal allograft survival: Have we made significant progress or is it time to rethink our analytic and therapeutic strategies? Am J Transplant. 2004;4(8):1289–95.PubMedCrossRef Meier-Kriesche HU, Schold JD, Kaplan B. Long-term renal allograft survival: Have we made significant progress or is it time to rethink our analytic and therapeutic strategies? Am J Transplant. 2004;4(8):1289–95.PubMedCrossRef
79.
Zurück zum Zitat Meier-Kriesche HU, et al. Lack of improvement in renal allograft survival despite a marked decrease in acute rejection rates over the most recent era. Am J Transplant. 2004;4(3):378–83.PubMedCrossRef Meier-Kriesche HU, et al. Lack of improvement in renal allograft survival despite a marked decrease in acute rejection rates over the most recent era. Am J Transplant. 2004;4(3):378–83.PubMedCrossRef
80.
Zurück zum Zitat Kwun J, et al. Patterns of De Novo Allo B cells and antibody formation in chronic cardiac allograft rejection after alemtuzumab treatment. Am J Transplant. 2012;12(10):2641–51.PubMedPubMedCentralCrossRef Kwun J, et al. Patterns of De Novo Allo B cells and antibody formation in chronic cardiac allograft rejection after alemtuzumab treatment. Am J Transplant. 2012;12(10):2641–51.PubMedPubMedCentralCrossRef
81.
Zurück zum Zitat Gareau A, et al. Contribution of B cells and antibody to cardiac allograft vasculopathy. Transplantation. 2009;88(4):470–7.PubMedCrossRef Gareau A, et al. Contribution of B cells and antibody to cardiac allograft vasculopathy. Transplantation. 2009;88(4):470–7.PubMedCrossRef
82.
Zurück zum Zitat Kwun J, et al. The role of B cells in solid organ transplantation. Semin Immunol. 2012;24(2):96–108.PubMedCrossRef Kwun J, et al. The role of B cells in solid organ transplantation. Semin Immunol. 2012;24(2):96–108.PubMedCrossRef
83.
Zurück zum Zitat Bachmann MF, et al. Distinct kinetics of cytokine production and cytolysis in effector and memory T cells after viral infection. Eur J Immunol. 1999;29(1):291–9.PubMedCrossRef Bachmann MF, et al. Distinct kinetics of cytokine production and cytolysis in effector and memory T cells after viral infection. Eur J Immunol. 1999;29(1):291–9.PubMedCrossRef
84.
Zurück zum Zitat Budd RC, et al. Distinction of virgin and memory lymphocytes-t stable acquisition of the Pgp-1 glycoprotein concomitant with antigenic-stimulation. J Immunol. 1987;138(10):3120–9.PubMed Budd RC, et al. Distinction of virgin and memory lymphocytes-t stable acquisition of the Pgp-1 glycoprotein concomitant with antigenic-stimulation. J Immunol. 1987;138(10):3120–9.PubMed
85.
Zurück zum Zitat Damle NK, et al. Differential Costimulatory Effects of Adhesion Molecules B7, Icam-1, Lfa-3, and Vcam-1 on Resting and Antigen-Primed Cd4 + Lymphocytes-T. J Immunol. 1992;148(7):1985–92.PubMed Damle NK, et al. Differential Costimulatory Effects of Adhesion Molecules B7, Icam-1, Lfa-3, and Vcam-1 on Resting and Antigen-Primed Cd4 + Lymphocytes-T. J Immunol. 1992;148(7):1985–92.PubMed
86.
Zurück zum Zitat Rogers PR, Dubey C, Swain SL. Qualitative changes accompany memory T cell generation: faster, more effective responses at lower doses of antigen. J Immunol. 2000;164(5):2338–46.PubMedCrossRef Rogers PR, Dubey C, Swain SL. Qualitative changes accompany memory T cell generation: faster, more effective responses at lower doses of antigen. J Immunol. 2000;164(5):2338–46.PubMedCrossRef
87.
Zurück zum Zitat Ford ML, Larsen CP. COvercoming the memory barrier in tolerance induction: molecular mimicry and functional heterogeneity among pathogen-specific T-cell populations. Curr Opin Organ Transplant. 2010;15(4):405–10.PubMedPubMedCentralCrossRef Ford ML, Larsen CP. COvercoming the memory barrier in tolerance induction: molecular mimicry and functional heterogeneity among pathogen-specific T-cell populations. Curr Opin Organ Transplant. 2010;15(4):405–10.PubMedPubMedCentralCrossRef
88.
Zurück zum Zitat Valujskikh A. The challenge of inhibiting alloreactive T-cell memory. Am J Transplant. 2006;6(4):647–51.PubMedCrossRef Valujskikh A. The challenge of inhibiting alloreactive T-cell memory. Am J Transplant. 2006;6(4):647–51.PubMedCrossRef
89.
Zurück zum Zitat Marco MRL et al. Post-transplant repopulation of naive and memory T cells in blood and lymphoid tissue after alemtuzumab-mediated depletion in heart-transplanted cynomolgus monkeys. Transpl Immunol. 2013;29(1–4):88–98.PubMedCrossRef Marco MRL et al. Post-transplant repopulation of naive and memory T cells in blood and lymphoid tissue after alemtuzumab-mediated depletion in heart-transplanted cynomolgus monkeys. Transpl Immunol. 2013;29(1–4):88–98.PubMedCrossRef
90.
Zurück zum Zitat Rao SP, et al. Human peripheral blood mononuclear cells exhibit heterogeneous CD52 expression levels and show differential sensitivity to alemtuzumab mediated cytolysis. PLoS One, 2012;7(6). Rao SP, et al. Human peripheral blood mononuclear cells exhibit heterogeneous CD52 expression levels and show differential sensitivity to alemtuzumab mediated cytolysis. PLoS One, 2012;7(6).
91.
Zurück zum Zitat Fischer A, et al. Severe combined immunodeficiency. A model disease for molecular immunology and therapy. Immunol Rev. 2005;203:98–109.PubMedCrossRef Fischer A, et al. Severe combined immunodeficiency. A model disease for molecular immunology and therapy. Immunol Rev. 2005;203:98–109.PubMedCrossRef
92.
Zurück zum Zitat Antoine C, et al. Long-term survival and transplantation of haemopoietic stem cells for immunodeficiencies: report of the European experience 1968–99. The Lancet. 2003;361(9357):553–60.CrossRef Antoine C, et al. Long-term survival and transplantation of haemopoietic stem cells for immunodeficiencies: report of the European experience 1968–99. The Lancet. 2003;361(9357):553–60.CrossRef
93.
Zurück zum Zitat Strout MP, Seropian S, Berliner N. Alemtuzumab as a bridge to allogeneic SCT in atypical hemophagocytic lymphohistiocytosis. Nature reviews. Clin Oncol. 2010;7(7):415–20. Strout MP, Seropian S, Berliner N. Alemtuzumab as a bridge to allogeneic SCT in atypical hemophagocytic lymphohistiocytosis. Nature reviews. Clin Oncol. 2010;7(7):415–20.
94.
Zurück zum Zitat Alinari L, et al. Alemtuzumab (Campath-1H) in the treatment of chronic lymphocytic leukemia. Oncogene. 2007;26(25):3644–53.PubMedCrossRef Alinari L, et al. Alemtuzumab (Campath-1H) in the treatment of chronic lymphocytic leukemia. Oncogene. 2007;26(25):3644–53.PubMedCrossRef
95.
Zurück zum Zitat Gartner F, et al. Lowering the alemtuzumab dose in reduced intensity conditioning allogeneic hematopoietic cell transplantation is associated with a favorable early intense natural killer cell recovery. CytoTherapy. 2013;15(10):1237–44.PubMedCrossRef Gartner F, et al. Lowering the alemtuzumab dose in reduced intensity conditioning allogeneic hematopoietic cell transplantation is associated with a favorable early intense natural killer cell recovery. CytoTherapy. 2013;15(10):1237–44.PubMedCrossRef
96.
Zurück zum Zitat Dunbar EM, et al. The relationship between circulating natural killer cells after reduced intensity conditioning hematopoietic stem cell transplantation and relapse-free survival and graft-versus-host disease. Hematol J. 2008;93(12):1852–8.CrossRef Dunbar EM, et al. The relationship between circulating natural killer cells after reduced intensity conditioning hematopoietic stem cell transplantation and relapse-free survival and graft-versus-host disease. Hematol J. 2008;93(12):1852–8.CrossRef
97.
Zurück zum Zitat Slatter MA, et al. Long-term immune reconstitution after anti-CD52-treated or anti-CD34-treated hematopoietic stem cell transplantation for severe T-lymphocyte immunodeficiency. J Allergy Clin Immunol. 2008;121(2):361–7.PubMedCrossRef Slatter MA, et al. Long-term immune reconstitution after anti-CD52-treated or anti-CD34-treated hematopoietic stem cell transplantation for severe T-lymphocyte immunodeficiency. J Allergy Clin Immunol. 2008;121(2):361–7.PubMedCrossRef
98.
99.
100.
Zurück zum Zitat Ferrara JLM, et al. Graft-versus-host disease. The Lancet. 2009;373(9674):1550–61.CrossRef Ferrara JLM, et al. Graft-versus-host disease. The Lancet. 2009;373(9674):1550–61.CrossRef
101.
Zurück zum Zitat Tey SK, et al. Pharmacokinetics and immunological outcomes of alemtuzumab-based treatment for steroid-refractory acute GvHD. Bone Marrow Transplant. 2016;51(8):1153–5.PubMedCrossRef Tey SK, et al. Pharmacokinetics and immunological outcomes of alemtuzumab-based treatment for steroid-refractory acute GvHD. Bone Marrow Transplant. 2016;51(8):1153–5.PubMedCrossRef
102.
Zurück zum Zitat Marsh RA, et al. Alemtuzumab levels impact acute GVHD, mixed chimerism, and lymphocyte recovery following alemtuzumab, fludarabine, and melphalan RIC HCT. Blood. 2016;127(4):503–12.PubMedCrossRef Marsh RA, et al. Alemtuzumab levels impact acute GVHD, mixed chimerism, and lymphocyte recovery following alemtuzumab, fludarabine, and melphalan RIC HCT. Blood. 2016;127(4):503–12.PubMedCrossRef
103.
Zurück zum Zitat Saraf SL, et al. Nonmyeloablative stem cell transplantation with alemtuzumab/low-dose irradiation to cure and improve the quality of life of adults with sickle cell disease. Biol Blood Marrow Transplant. 2016;22(3):441–8.PubMedCrossRef Saraf SL, et al. Nonmyeloablative stem cell transplantation with alemtuzumab/low-dose irradiation to cure and improve the quality of life of adults with sickle cell disease. Biol Blood Marrow Transplant. 2016;22(3):441–8.PubMedCrossRef
Metadaten
Titel
The immunological function of CD52 and its targeting in organ transplantation
verfasst von
Yang Zhao
Huiting Su
Xiaofei Shen
Junfeng Du
Xiaodong Zhang
Yong Zhao
Publikationsdatum
10.03.2017
Verlag
Springer International Publishing
Erschienen in
Inflammation Research / Ausgabe 7/2017
Print ISSN: 1023-3830
Elektronische ISSN: 1420-908X
DOI
https://doi.org/10.1007/s00011-017-1032-8

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