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Philosophical Transactions of the Royal Society B: Biological Sciences
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CAMPATH: from concept to clinic

Published:16 August 2005https://doi.org/10.1098/rstb.2005.1702

    Abstract

    Lymphocyte depletion has a long history in the area of therapeutic immunosuppression. CAMPATH-1H (alemtuzumab) was generated in an attempt to replace anti-lymphocyte globulins in the transplant arena. Its efficacy in killing lymphocytes has established it as a licensed drug for the management of chronic lymphocyte leukaemia. Short-term therapy with alemtuzumab has demonstrated long-term benefit in a number of autoimmune conditions. This drug has the potential to facilitate recruitment of tolerance processes so enabling drug minimization in transplantation, autoimmune and hypersensitivity diseases.

    References

    • Axelrod D, Leventhal J.R, Gallon L.G, Parker M.A& Kaufman D.B. 2005Reduction of CMV disease with steroid-free immunosuppresssion in simultaneous pancreas-kidney transplant recipients. Am. J. Transplant. 5, 1423–1429. Crossref, PubMed, ISI, Google Scholar
    • Bruggemann M, Free J, Diamond A, Howard J, Cobbold S& Waldmann H. 1986Immunoglobulin heavy chain locus of the rat: striking homology to mouse antibody genes. Proc. Natl Acad. Sci. USA. 83, 6075–6079. Crossref, PubMed, ISI, Google Scholar
    • Bruggemann M, Williams G.T, Bindon C.I, Clark M.R, Walker M.R, Jefferis R, Waldmann H& Neuberger M.S. 1987Comparison of the effector functions of human immunoglobulins using a matched set of chimeric antibodies. J. Exp. Med. 166, 1351–1361. Crossref, PubMed, ISI, Google Scholar
    • Bruggemann M, Winter G, Waldmann H& Neuberger M.S. 1989The immunogenicity of chimeric antibodies. J. Exp. Med. 170, 2153–2157. Crossref, PubMed, ISI, Google Scholar
    • Calne R, et al.1999Campath IH allows low-dose cyclosporine monotherapy in 31 cadaveric renal allograft recipients. Transplantation. 68, 1613–1616. Crossref, PubMed, ISI, Google Scholar
    • Ciancio G, et al.2004The use of Campath-1H as induction therapy in renal transplantation: preliminary results. Transplantation. 78, 426–433. Crossref, PubMed, ISI, Google Scholar
    • Clark M, Hale G& Waldmann H. 1985Interaction of rat monoclonal antibodies with human killer cells. Adv. Exp. Med. Biol. 186, 797–803. PubMed, ISI, Google Scholar
    • Cobbold S.P, Jayasuriya A, Nash A, Prospero T.D& Waldmann H. 1984Therapy with monoclonal antibodies by elimination of T-cell subsets in vivo. Nature. 312, 548–551. Crossref, PubMed, ISI, Google Scholar
    • Cobbold S.P, Martin G, Qin S& Waldmann H. 1986Monoclonal antibodies to promote marrow engraftment and tissue graft tolerance. Nature. 323, 164–166. Crossref, PubMed, ISI, Google Scholar
    • Coles A.J, et al.1999Pulsed monoclonal antibody treatment and autoimmune thyroid disease in multiple sclerosis. Lancet. 354, 1691–1695. Crossref, PubMed, ISI, Google Scholar
    • Dyer M.J, Hale G, Hayhoe F.G& Waldmann H. 1989Effects of CAMPATH-1 antibodies in vivo in patients with lymphoid malignancies: influence of antibody isotype. Blood. 73, 1431–1439. Crossref, PubMed, ISI, Google Scholar
    • Gerritsen W.R, Wagemaker G, Jonker M, Kenter M.J, Wielenga J.J, Hale G, Waldmann H& van Bekkum D.W. 1988The repopulation capacity of bone marrow grafts following pretreatment with monoclonal antibodies against T lymphocytes in rhesus monkeys. Transplantation. 45, 301–307. Crossref, PubMed, ISI, Google Scholar
    • Gowans J.L, McGregor G.D& Cowen D.M. 1962Initiation of immune responses by small lymphocytes. Nature. 196, 651–655. Crossref, PubMed, ISI, Google Scholar
    • Gruessner R.W, Kandaswamy R, Humar A, Gruessner A.C& Sutherland D.E. 2005Calcineurin inhibitor- and steroid-free immunosuppression in pancreas-kidney and solitary pancreas transplantation. Transplantation. 79, 1184–1189. Crossref, PubMed, ISI, Google Scholar
    • Haas R.J, et al.1980Antibody incubation of human marrow graft for prevention of graft versus host disease. Blut. 40, 387–397. Crossref, PubMed, Google Scholar
    • Hale G& Waldmann H. 1996Recent results using CAMPATH-1 antibodies to control GVHD and graft rejection. Bone Marrow Transplant. 17, 305–308. PubMed, ISI, Google Scholar
    • Hale G, Bright S, Chumbley G, Hoang T, Metcalf D, Munro A.J& Waldmann H. 1983Removal of T cells from bone marrow for transplantation: a monoclonal antilymphocyte antibody that fixes human complement. Blood. 62, 873–882. Crossref, PubMed, ISI, Google Scholar
    • Hale G, Cobbold S.P, Waldmann H, Easter G, Matejtschuk P& Coombs R.R. 1987Isolation of low-frequency class-switch variants from rat hybrid myelomas. J. Immunol. Methods. 103, 59–67. Crossref, PubMed, ISI, Google Scholar
    • Hale G, Dyer M.J, Clark M.R, Phillips J.M, Marcus R, Riechmann L, Winter G& Waldmann H. 1988Remission induction in non-Hodgkin lymphoma with reshaped human monoclonal antibody CAMPATH-1H. Lancet. 2, 1394–1399. Crossref, PubMed, ISI, Google Scholar
    • Hale G, Cobbold S, Novitzky N, Bunjes D, Willemze R, Prentice H.G, Milligan D, MacKinnon S& Waldmann H. 2001CAMPATH-1 antibodies in stem-cell transplantation. Cytotherapy. 3, 145–164. Crossref, PubMed, ISI, Google Scholar
    • Hale G, Slavin S, Goldman J.M, Mackinnon S, Giralt S& Waldmann H. 2002Alemtuzumab (Campath-1H) for treatment of lymphoid malignancies in the age of nonmyeloablative conditioning?. Bone Marrow Transplant. 30, 797–804. Crossref, PubMed, ISI, Google Scholar
    • Hamblin M, et al.1996Campath-1G in vivo confers a low incidence of graft-versus-host disease associated with a high incidence of mixed chimaerism after bone marrow transplantation for severe aplastic anaemia using HLA-identical sibling donors. Bone Marrow Transplant. 17, 819–824. PubMed, ISI, Google Scholar
    • Jacobs P, Wood L, Fullard L, Waldmann H& Hale G. 1994T cell depletion by exposure to Campath-1G in vitro prevents graft-versus-host disease. Bone Marrow Transplant. 13, 763–769. PubMed, ISI, Google Scholar
    • Kato T, et al.2005Intestinal transplantation in children: a summary of clinical outcomes and prognostic factors in 108 patients from a single center. J. Gastrointest. Surg. 9, 75–89.discussion 89. Crossref, PubMed, ISI, Google Scholar
    • Keating M.J, et al.2002Therapeutic role of alemtuzumab (Campath-1H) in patients who have failed fludarabine: results of a large international study. Blood. 99, 3554–3561. Crossref, PubMed, ISI, Google Scholar
    • Kirk A.D, et al.2003Results from a human renal allograft tolerance trial evaluating the humanized CD52-specific monoclonal antibody alemtuzumab (CAMPATH-1H). Transplantation. 76, 120–129. Crossref, PubMed, ISI, Google Scholar
    • Knechtle S.J, et al.1997FN18-CRM9 immunotoxin promotes tolerance in primate renal allografts. Transplantation. 63, 1–6. Crossref, PubMed, ISI, Google Scholar
    • Knechtle S.J, Fernandez L.A, Pirsch J.D, Becker B.N, Chin L.T, Becker Y.T, Odorico J.S, D'Alessandro A.M& Sollinger H.W. 2004Campath-1H in renal transplantation: The University of Wisconsin experience. Surgery. 136, 754–760. Crossref, PubMed, ISI, Google Scholar
    • Kohler G& Milstein C. 1975Continuous cultures of fused cells secreting antibody of predefined specificity. Nature. 256, 495–497. Crossref, PubMed, ISI, Google Scholar
    • Kolb H.J, Storb R, Graham T.C, Kolb H& Thomas E.D. 1973Antithymocyte serum and methotrexate for control of graft-versus-host disease in dogs. Transplantation. 16, 17–23. Crossref, PubMed, ISI, Google Scholar
    • Korngold R& Sprent J. 1985Surface markers of T cells causing lethal graft-vs-host disease to class I vs class II H-2 differences. J. Immunol. 135, 3004–3010. PubMed, ISI, Google Scholar
    • Kottaridis P.D, et al.2001In vivo CAMPATH-1H prevents GvHD following nonmyeloablative stem-cell transplantation. Cytotherapy. 3, 197–201. Crossref, PubMed, ISI, Google Scholar
    • Lance E.M& Medawar P.B. 1968Survival of skin heterografts under treatment with antilymphocytic serum. Lancet. 1, 1174–1176. Crossref, PubMed, ISI, Google Scholar
    • Lance E.M& Medawar P. 1969Quantitative studies on tissue transplantation immunity. IX. Induction of tolerance with antilymphocytic serum. Proc. R Soc. B. 173, 447–473. Link, ISI, Google Scholar
    • Lance E.M& Medawar P.B. 1970Immunosuppressive effects of heterologous antilymphocyte serum in monkeys. Lancet. 1, 167–170. Crossref, PubMed, ISI, Google Scholar
    • Lockwood C.M, Thiru S, Stewart S, Hale G, Isaacs J, Wraight P, Elliott J& Waldmann H. 1996Treatment of refractory Wegener's granulomatosis with humanized monoclonal antibodies. QJM. 89, 903–912. Crossref, PubMed, Google Scholar
    • Mathieson P.W, Cobbold S.P, Hale G, Clark M.R, Oliveira D.B, Lockwood C.M& Waldmann H. 1990Monoclonal-antibody therapy in systemic vasculitis. N. Engl. J. Med. 323, 250–254. Crossref, PubMed, ISI, Google Scholar
    • McGregor D.D& Gowans J.L. 1964Survival of homografts of skin in rats depleted of lymphocytes by chronic drainage from the thoracic duct. Lancet. 15, 629–632. Crossref, Google Scholar
    • Perez-Simon J.A, et al.2002Nonmyeloablative transplantation with or without alemtuzumab: comparison between 2 prospective studies in patients with lymphoproliferative disorders. Blood. 100, 3121–3127. Crossref, PubMed, ISI, Google Scholar
    • Rebello P.R, Hale G, Friend P.J, Cobbold S.P& Waldmann H. 1999Anti-globulin responses to rat and humanized CAMPATH-1 monoclonal antibody used to treat transplant rejection. Transplantation. 68, 1417–1420. Crossref, PubMed, ISI, Google Scholar
    • Riechmann L, Clark M, Waldmann H& Winter G. 1988Reshaping human antibodies for therapy. Nature. 332, 323–327. Crossref, PubMed, ISI, Google Scholar
    • Shapiro R, et al.2005Kidney transplantation under minimal immunosuppression after pretransplant lymphoid depletion with Thymoglobulin or Campath. J. Am. Coll. Surg. 200, 505–515. Crossref, PubMed, ISI, Google Scholar
    • Tzakis A.G, et al.2004Preliminary experience with alemtuzumab (Campath-1H) and low-dose tacrolimus immunosuppression in adult liver transplantation. Transplantation. 77, 1209–1214. Crossref, PubMed, ISI, Google Scholar
    • Waldmann H, et al.1984Elimination of graft-versus-host disease by in-vitro depletion of alloreactive lymphocytes with a monoclonal rat anti-human lymphocyte antibody (CAMPATH-1). Lancet. 2, 483–486. Crossref, PubMed, ISI, Google Scholar
    • Watson C.J, et al.2005Alemtuzumab (CAMPATH 1H) induction therapy in cadaveric kidney transplantation: efficacy and safety at five years. Am. J. Transplant. 5, 1347–1353. Crossref, PubMed, ISI, Google Scholar
    • Weiden P.L, Doney K, Storb R& Thomas E.D. 1979Antihuman thymocyte globulin for prophylaxis of graft-versus-host disease. A randomized trial in patients with leukemia treated with HLA-identical sibling marrow grafts. Transplantation. 27, 227–230. Crossref, PubMed, ISI, Google Scholar
    • Willemze R, Richel D.J, Falkenburg J.H, Hale G, Waldmann H, Zwaan F.E& Fibbe W.E. 1992In vivo use of Campath-1G to prevent graft-versus-host disease and graft rejection after bone marrow transplantation. Bone Marrow Transplant. 9, 255–261. PubMed, ISI, Google Scholar
    • Xia M.Q, Tone M, Packman L, Hale G& Waldmann H. 1991Characterization of the CAMPATH-1 (CDw52) antigen: biochemical analysis and cDNA cloning reveal an unusually small peptide backbone. Eur. J. Immunol. 21, 1677–1684. Crossref, PubMed, ISI, Google Scholar
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