Mode of action and clinical studies with alemtuzumab

Experimental Neurology

Volumn 262, Issue Part A, 2014, Pages 37-43

  Jones, Joanne L ^a   Coles, Alasdair J ^a  

^a Cambridge Biomedical Campus ^*  (United Kingdom)

Author keywords

Alemtuzumab; Clinical trials; Immunotherapy; Multiple sclerosis

Indexed keywords

ACICLOVIR; ALEMTUZUMAB; ANTIHISTAMINIC AGENT; ANTIPYRETIC AGENT; BETA INTERFERON; BETA1A INTERFERON; BRAIN DERIVED NEUROTROPHIC FACTOR; CILIARY NEUROTROPHIC FACTOR; CORTICOSTEROID; CREATININE; CYCLOPHOSPHAMIDE; DIURETIC AGENT; GLATIRAMER; IMMUNOGLOBULIN; INTERLEUKIN 21; METHYLPREDNISOLONE; NATALIZUMAB; PARACETAMOL; PLATELET DERIVED GROWTH FACTOR; RITUXIMAB; STEROID; THIAMAZOLE; CD52 ANTIGEN; GLYCOPROTEIN; LEUKOCYTE ANTIGEN; MONOCLONAL ANTIBODY; TUMOR ANTIGEN;

ANTIINFLAMMATORY ACTIVITY; AUSTRALIA; AUTOIMMUNE DISEASE; AUTOIMMUNITY; B LYMPHOCYTE; BRAZIL; BREAST FEEDING; CANADA; CAUSE OF DEATH; CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; CYTOKINE RELEASE; DISEASE DURATION; DISEASE EXACERBATION; DRUG ACCUMULATION; DRUG EFFICACY; DRUG MECHANISM; DRUG SAFETY; EUROPEAN UNION; FEVER; FINE NEEDLE ASPIRATION BIOPSY; GLOMERULONEPHRITIS; GRAVES DISEASE; HEADACHE; HEMATURIA; HEMODIALYSIS; HEMOLYTIC ANEMIA; HERPES SIMPLEX; HERPES ZOSTER; HUMAN; HYPOTHYROIDISM; IDIOPATHIC THROMBOCYTOPENIC PURPURA; INFECTION; INFECTION RISK; KIDNEY FAILURE; KIDNEY TRANSPLANTATION; LONG TERM CARE; LYMPHOCYTE DEPLETION; MALAISE; MEMBRANOUS GLOMERULONEPHRITIS; MEXICO; MULTIPLE CYCLE TREATMENT; MULTIPLE SCLEROSIS; NEUROLOGIC DISEASE; NEUTROPENIA; NONHUMAN; NUCLEAR MAGNETIC RESONANCE IMAGING; PANCYTOPENIA; PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PLASMAPHERESIS; PNEUMONIA; PREGNANCY; PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; PROTEINURIA; RASH; RESPIRATORY TRACT INFECTION; REVIEW; RISK ASSESSMENT; RISK REDUCTION; SEPSIS; SINGLE DRUG DOSE; T LYMPHOCYTE; THYROID CARCINOMA; THYROID FUNCTION; THYROID NODULE; THYROID PAPILLARY CARCINOMA; THYROIDECTOMY; TREATMENT OUTCOME; TUMOR ABLATION; URINALYSIS; URINARY TRACT INFECTION; URTICARIA; VACCINATION; ANIMAL; CLINICAL TRIAL (TOPIC); IMMUNOLOGY;

ANIMALS; ANTIBODIES, MONOCLONAL, HUMANIZED; ANTIGENS, CD; ANTIGENS, NEOPLASM; CLINICAL TRIALS AS TOPIC; GLYCOPROTEINS; HUMANS; MULTIPLE SCLEROSIS;

EID: 84908608431     PISSN: 00144886     EISSN: 10902430     Source Type: Journal    
DOI: 10.1016/j.expneurol.2014.04.018     Document Type: Review

References (50)

1. Azzopardi L., Thompson S.A.J., Harding K.E., Cossburn M., Robertson N., Compston A., Coles A.J., Jones J.L. Predicting autoimmunity after alemtuzumab treatment of multiple sclerosis. J. Neurol. Neurosurg. Psychiatry 2014, 1-4. 10.1136/jnnp-2013-307042.
2. Baccala R., Theofilopoulos A.N. The new paradigm of T-cell homeostatic proliferation-induced autoimmunity. Trends Immunol. 2005, 26:5-8.
3. Bandala-Sanchez E., Zhang Y., Reinwald S., Dromey J.A., Lee B.H., Qian J., Bohmer R.M., Harrison L.C. T cell regulation mediated by interaction of soluble CD52 with the inhibitory receptor Siglec-10. Nat. Immunol. 2013, 14:741-748.
4. Berker D., Isik S., Ozuguz U., Tutuncu Y.A., Kucukler K., Akbaba G., Aydin Y., Guler S. Prevalence of incidental thyroid cancer and its ultrasonographic features in subcentimeter thyroid nodules of patients with hyperthyroidism. Endocrine 2011, 39:13-20.
5. Broadley S.A., Deans J., Sawcer S.J., Clayton D., Compston D.A. Autoimmune disease in first-degree relatives of patients with multiple sclerosis. A UK survey. Brain 2000, 123(Pt 6):1102-1111.
6. Button T., Altmann D., Tozer D., Dalton C., Hunter K., Compston A., Coles A., Miller D. Magnetization transfer imaging in multiple sclerosis treated with alemtuzumab. Mult. Scler. 2013, 19(2):241-244. 10.1177/1352458512444915.
7. Cho B.K., Rao V.P., Ge Q., Eisen H.N., Chen J. Homeostasis-stimulated proliferation drives naive T cells to differentiate directly into memory T cells. J. Exp. Med. 2000, 192:549-556.
8. Cohen J.A., Coles A.J., Arnold D.L., Confavreux C., Fox E.J., Hartung H.P., Havrdova E., Selmaj K.W., Weiner H.L., Fisher E., 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):1819-1828. (Epub 2012 Nov 1). 10.1016/S0140-6736(12)61769-3.
9. Coles A.J., Wing M.G., Molyneux P., Paolillo A., Davie C.M., Hale G., Miller D., Waldmann H., Compston A. Monoclonal antibody treatment exposes three mechanisms underlying the clinical course of multiple sclerosis. Ann. Neurol. 1999, 46:296-304.
10. Coles A.J., Cox A., Page E., Jones J., Trip S.A., Deans J., Seaman S., Miller D.H., Hale G., Waldmann H., et al. The window of therapeutic opportunity in multiple sclerosis. J. Neurol. 2005, 253:98-108.
11. Coles A.J., Cox A., Le Page E., Jones J., Trip S.A., Deans J., Seaman S., Miller D.H., Hale G., Waldmann H., et al. The window of therapeutic opportunity in multiple sclerosis: evidence from monoclonal antibody therapy. J. Neurol. 2006, 253:98-108.
12. Coles A.J., Compston D.A., Selmaj K.W., Lake S.L., Moran S., Margolin D.H., Norris K., Tandon P.K. Alemtuzumab vs. interferon beta-1a in early multiple sclerosis. N. Engl. J. Med. 2008, 359:1786-1801.
13. Coles A.J., Fox E., Vladic A., Gazda S.K., Brinar V., Selmaj K.W., Bass A.D., Wynn D.R., Margolin D.H., Lake S.L., et al. Alemtuzumab versus interferon beta-1a in early relapsing-remitting multiple sclerosis: post-hoc and subset analyses of clinical efficacy outcomes. Lancet Neurol. 2011, 10:338-348.
14. Coles A.J., Fox E., Vladic A., Gazda S.K., Brinar V., Selmaj K.W., Skoromets A., Stolyarov I., Bass A., Sullivan H., et al. Alemtuzumab more effective than interferon beta-1a at 5-year follow-up of CAMMS223 clinical trial. Neurology 2012, 78:1069-1078.
15. Coles A.J., Twyman C.L., Arnold D.L., Cohen J.A., Confavreux C., Fox E.J., Hartung H.P., Havrdova E., Selmaj K.W., Weiner H.L., et al. Alemtuzumab for patients with relapsing multiple sclerosis after disease-modifying therapy: a randomised controlled phase 3 trial. Lancet 2012, 380(9856):1829-1839. (Epub 2012 Nov 1). 10.1016/S0140-6736(12)61768-1.
16. Cossburn M., Baker K.E., Ingram G., Pickersgill T.P., Robertson N.P. 129 Serum IL-21 as a biomarker in multiple sclerosis. J. Neurol. Neurosurg. Psychiatry 2012, 83:e1.
17. Dick A.D., Meyer P., James T., Forrester J.V., Hale G., Waldmann H., Isaacs J.D. Campath-1H therapy in refractory ocular inflammatory disease. Br. J. Ophthalmol. 2000, 84:107-109.
18. Gleeson P.A., Toh B.H., van D.I. Organ-specific autoimmunity induced by lymphopenia. Immunol. Rev. 1996, 149:97-125.
19. Goldrath A.W., Bogatzki L.Y., Bevan M.J. Naive T cells transiently acquire a memory-like phenotype during homeostasis-driven proliferation. J. Exp. Med. 2000, 192:557-564.
20. Goodin D.S., Frohman E.M., Garmany G.P., Halper J., Likosky W.H., Lublin F.D., Silberberg D.H., Stuart W.H., van den Noort S. Disease modifying therapies in multiple sclerosis: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and the MS Council for Clinical Practice Guidelines. Neurology 2002, 58:169-178.
21. Havrdova E., D.L.A., Cohen J.A., Coles A.J., Fox E.J., Hartung H.-P., Selmaj K., Weiner H.L., Palmer J., Margolin D.H., Oyuela P., Panzara M.A., Compston D.A.S. Infection risk with alemtuzumab in patients with relapsing remitting multiple sclerosis: pooled results from the CARE-MS I and CARE-MS II trials. Mult. Scler. 2013, 19:74-558.
22. Heinzlef O., Alamowitch S., Sazdovitch V., Chillet P., Joutel A., Tournier-Lasserve E., Roullet E. Autoimmune diseases in families of French patients with multiple sclerosis. Acta Neurol. Scand. 2000, 101:36-40.
23. Hill-Cawthorne G.A., Button T., Tuohy O., Jones J.L., May K., Somerfield J., Green A., Giovannoni G., Compston D.A., Fahey M.T., et al. Long term lymphocyte reconstitution after alemtuzumab treatment of multiple sclerosis. J. Neurol. Neurosurg. Psychiatry 2012, 83:298-304. (Epub 2011 Nov 5). 10.1136/jnnp-2011-300826.
24. Hu Y., Turner M.J., Shields J., Gale M.S., Hutto E., Roberts B.L., Siders W.M., Kaplan J.M. Investigation of the mechanism of action of alemtuzumab in a human CD52 transgenic mouse model. Immunology 2009, 128:260-270.
25. Isaacs J.D., Hale G., Waldmann H., Dick A.D., Haynes R., Forrester J.V., Watson P., Meyer P.A. Monoclonal antibody therapy of chronic intraocular inflammation using Campath-1H. Br. J. Ophthalmol. 1995, 79:1054-1055.
26. Isaacs J.D., Hazleman B.L., Chakravarty K., Grant J.W., Hale G., Waldmann H. Monoclonal antibody therapy of diffuse cutaneous scleroderma with CAMPATH-1H. J. Rheumatol. 1996, 23:1103-1106.
27. Isaacs J.D., Manna V.K., Rapson N., Bulpitt K.J., Hazleman B.L., Matteson E.L., St Clair E.W., Schnitzer T.J., Johnston J.M. CAMPATH-1H in rheumatoid arthritis-an intravenous dose-ranging study. Br. J. Rheumatol. 1996, 35:231-240.
28. Jones J.L., Phuah C.L., Cox A.L., Thompson S.A., Ban M., Shawcross J., Walton A., Sawcer S.J., Compston A., Coles A.J. IL-21 drives secondary autoimmunity in patients with multiple sclerosis, following therapeutic lymphocyte depletion with alemtuzumab (Campath-1H). J. Clin. Investig. 2009, 119:2052-2061.
29. Jones J.L., Anderson J.M., Phuah C.L., Fox E.J., Selmaj K., Margolin D., Lake S.L., Palmer J., Thompson S.J., Wilkins A., et al. Improvement in disability after alemtuzumab treatment of multiple sclerosis is associated with neuroprotective autoimmunity. Brain 2010, 133:2232-2247.
30. Jones J.L., Thompson S.A., Loh P., Davies J.L., Tuohy O.C., Curry A.J., Azzopardi L., Hill-Cawthorne G., Fahey M.T., Compston A., et al. Human autoimmunity after lymphocyte depletion is caused by homeostatic T-cell proliferation. Proc. Natl. Acad. Sci. U. S. A. 2013, 110:20200-20205.
31. Kappos L., Li D., Calabresi P.A., O'Connor P., Bar-Or A., Barkhof F., Yin M., Leppert D., Glanzman R., Tinbergen J., et al. Ocrelizumab in relapsing-remitting multiple sclerosis: a phase 2, randomised, placebo-controlled, multicentre trial. Lancet 2011, 378:1779-1787.
32. Kassiotis G., Zamoyska R., Stockinger B. Involvement of avidity for major histocompatibility complex in homeostasis of naive and memory T cells. J. Exp. Med. 2003, 197:1007-1016.
33. Khoruts A., Fraser J. A causal link between lymphopenia and autoimmunity. Immunol. Lett. 2005, 98:23-31.
34. Kim W.B., Han S.-M., Kim T.Y., Nam-Goong I.S., Gong G., Lee H.K., Hong S.J., Shong Y.K. Ultrasonographic screening for detection of thyroid cancer in patients with Graves' disease. Clin. Endocrinol. 2004, 60:719-725.
35. King C., Ilic A., Koelsch K., Sarvetnick N. Homeostatic expansion of T cells during immune insufficiency generates autoimmunity. Cell 2004, 117:265-277.
36. Kraimps J.L., Bouin-Pineau M.H., Mathonnet M., De Calan L., Ronceray J., Visset J., Marechaud R., Barbier J. Multicentre study of thyroid nodules in patients with Graves' disease. Br. J. Surg. 2000, 87:1111-1113.
37. Krupica T., Fry T.J., Mackall C.L. Autoimmunity during lymphopenia: a two-hit model. Clin. Immunol. 2006, 120:121-128.
38. Kurtzke J.F. Rating neurologic impairment in multiple-sclerosis-an Expanded Disability Status Scale (EDSS). Neurology 1983, 33:1444-1452.
39. Lockwood C.M., Hale G., Waldman H., Jayne D.R. Remission induction in Behcet's disease following lymphocyte depletion by the anti-CD52 antibody CAMPATH 1-H. Rheumatology (Oxford) 2003, 42:1539-1544.
40. Lycke J., D.L.A., Cohen J.A., Coles A.J., Fox E.J., Hartung H.-P., Havrdova E., Selmaj K.W., Weiner H.L., Palmer J., Margolin D.H., Oyuela P., Panzara M.A., Compston D.A.S. Adverse event profile of alemtuzumab in active relapsing remitting multiple sclerosis patients who participated in the CARE-MS studies: three-year follow-up. Mult. Scler. 2013, 19:74-558.
41. McCarthy C.L., Tuohy O., Compston D.A., Kumararatne D.S., Coles A.J., Jones J.L. Immune competence after alemtuzumab treatment of multiple sclerosis. Neurology 2013, 81:872-876.
42. Moreau T., Coles A., Wing M., Isaacs J., Hale G., Waldmann H., Compston A. Transient increase in symptoms associated with cytokine release in patients with multiple sclerosis. Brain 1996, 119(Pt 1):225-237.
43. Moxham V.F., Karegli J., Phillips R.E., Brown K.L., Tapmeier T.T., Hangartner R., Sacks S.H., Wong W. Homeostatic proliferation of lymphocytes results in augmented memory-like function and accelerated allograft rejection. J. Immunol. 2008, 180:3910-3918.
44. Murali-Krishna K., Ahmed R. Cutting edge: naive T cells masquerading as memory cells. J. Immunol. 2000, 165:1733-1737.
45. Newman D.K., Isaacs J.D., Watson P.G., Meyer P.A., Hale G., Waldmann H. Prevention of immune-mediated corneal graft destruction with the anti-lymphocyte monoclonal antibody, CAMPATH-1H. Eye Lond. 1995, 9(Pt 5):564-569.
46. Thompson S.A., Jones J.L., Cox A.L., Compston D.A., Coles A.J. B-cell reconstitution and BAFF after alemtuzumab (Campath-1H) treatment of multiple sclerosis. J. Clin. Immunol. 2010, 30(1):99-105. (Epub 2009 Sep 10). 10.1007/s10875-009-9327-3.
47. Wing M.G., Moreau T., Greenwood J., Smith R.M., Hale G., Isaacs J., Waldmann H., Lachmann P.J., Compston A. Mechanism of first-dose cytokine-release syndrome by CAMPATH 1-H: involvement of CD16 (FcgammaRIII) and CD11a/CD18 (LFA-1) on NK cells. J. Clin. Invest. 1996, 98:2819-2826.
48. Wu Z., Bensinger S.J., Zhang J., Chen C., Yuan X., Huang X., Markmann J.F., Kassaee A., Rosengard B.R., Hancock W.W., et al. Homeostatic proliferation is a barrier to transplantation tolerance. Nat. Med. 2004, 10:87-92.
49. Wynn D., D.L.A., Cohen J.A., Coles A.J., Fox E.J., Hartung H.-P., Havrdova E., Selmaj K.W., Weiner H.L., Palmer J., Margolin D.H., Oyuela P., Panzara M.A., Compston D.A.S. Detection, incidence and management of glomerulonephritis in the alemtuzumab clinical development programme. Mult. Scler. 2013, 19:74-558.
50. Zandman-Goddard G., Shoenfeld Y. HIV and autoimmunity. Autoimmun. Rev. 2002, 1:329-337.