First clinical trials of a new heteropolymer technology agent in normal healthy volunteers and patients with systemic lupus erythematosus: Safety and proof of principle of the antigen-heteropolymer ETI-104

Annals of the Rheumatic Diseases

Volumn 63, Issue 9, 2004, Pages 1104-1112

  Iking Konert, C ^a   Stocks, S ^a   Weinsberg, F ^b   Engelbrecht, R ^a   Bleck, E ^a   Perniok, A ^c   Fischer Betz, R ^a   Pincus, S ^d   Nardone, L ^d   Schneider, M ^a  

^a HEINRICH HEINE UNIVERSITY   (Germany)

^b FOCUS Clinical Drug Development GmbH   (Germany)

^c UNIVERSITY OF COLOGNE   (Germany)

^d Elusys Therapeutics Inc   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIBODY CONJUGATE; DNA ANTIBODY; DOUBLE STRANDED DNA; ETI 104; UNCLASSIFIED DRUG;

ADULT; ANTIBODY BLOOD LEVEL; ANTIGEN ANTIBODY REACTION; ARTHRALGIA; ARTICLE; BINDING AFFINITY; BLOOD ANALYSIS; CLINICAL ARTICLE; CLINICAL TRIAL; COMMON COLD; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DEMOGRAPHY; DIARRHEA; DRUG BINDING; DRUG CLEARANCE; DRUG SAFETY; DRUG TOLERABILITY; ERYTHROCYTE; FEMALE; FLUORESCENCE ACTIVATED CELL SORTING; HEADACHE; HEMATOMA; HUMAN; HUMAN CELL; IN VITRO STUDY; IN VIVO STUDY; MALE; PRIORITY JOURNAL; RHINITIS; SINGLE DRUG DOSE; SKIN MANIFESTATION; SORE THROAT; SYSTEMIC LUPUS ERYTHEMATOSUS; URINALYSIS; VOMITING;

ADULT; ANTIBODIES, ANTINUCLEAR; ANTIBODY AFFINITY; CELLS, CULTURED; DNA; ERYTHROCYTES; FEMALE; HUMANS; IMMUNOCONJUGATES; LUPUS ERYTHEMATOSUS, SYSTEMIC; MALE; MIDDLE AGED; RECEPTORS, COMPLEMENT 3B;

EID: 4344630370     PISSN: 00034967     EISSN: None     Source Type: Journal    
DOI: 10.1136/ard.2003.016691     Document Type: Article

References (48)

1. Nelson RA. The immune-adherence phenomenon. An immunological specific reaction between micro-organisms and erythrocytes leading to enhanced phagocytosis. Science 1953;118:733-77.
2. Nelson RA. The immune-adherence phenomenon. A hypothetical role of erythrocytes in defense against bacteria and viruses. Proc R Soc Med 1955;49:55-8.
3. Fearon DT. Identification of the membrane glycoprotein that is the C3b receptor of the human erythrocyte, polymorphonuclear leukocyte, B lymphocyte, and monocyte. J Exp Med 1980;152:20-30.
4. Schifferli JA, Taylor RP. Physiological and pathological aspects of circulating immune complexes. Kidney Int 1989;35:993-1003.
5. Cornacoff JB, Hebert LA, Smead WL, VanAman ME, Birmingham DJ, Waxman FJ. Primate erythrocyte-immune complex clearing mechanism. J Clin Invest 1983;71:236-43.
6. Hebert LA, Cosio FG. The erythrocyte-immune complex-glomerulonephritis connection in man. Kidney Int 1987;31:877-85.
7. Lindorfer MA, Hahn CS, Foley PL, Taylor RP. Heteropolymer-mediated clearance of immune complexes via erythrocyte CR1: mechanisms and applications. Immunol Rev 2001;183:10-24.
8. Taylor RP, Sutherland WM, Martin EN, Ferguson PJ, Reinagel ML, Gilbert E, et al. Bispecific monoclonal antibody complexes bound to primate erythrocyte complement receptor 1 facilitates virus clearance in a monkey model. J Immunol 1997;158:842-50.
9. Ferguson PJ, Reist CJ, Martin EN, Johnson C, Greene KL, Kuhn S, Niebur J, et al. Antigen-based heteropolymers: a potential therapy for binding and clearing autoantibodies via erythrocyte CR1. Arthritis Rheum 1995;38:190-200.
10. Lindorfer MA, Schuman TA, Craig ML, Martin, EN, Taylor RP. A bispecific dsDNA-monoclonal antibody construct for clearance of anti-dsDNA IgG in systemic lupus erythematosus. Immunol Methods 2001;248:125-38.
11. Pincus SE, Lukacher N, Mohamed N, Sesay M, Zabinski R, Ebelle R, et al. Evaluation of antigen-based heteropolymer for treatment of systemic lupus erythematosus in a nonhuman primate model. Clin Immunol 2002;105:141-54.
12. Hecht B, Siegel N, Adler M, Kashgarian M, Hayslett JP. Prognostic indices in lupus nephritis. Medicine (Baltimore) 1976;55:163-81.
13. Gauthier VJ, Emlen JW. In: Wallace DJ, Hahn BH, eds. Dubois' Lupus Erythematosus, 5th ed. Baltimore: Williams and Wilkins, 1997:207.
14. Stollar BD. Anti-DNA antibodies. Clin Immunol Allergy 1981;1:243.
15. Tan EM, Schur PH, Carr RI, Kunkel HG. Deoxyribonucleic acid (DNA) and antibodies to DNA in the serum of patients with systemic erythematosus. J Clin Invest 1966;45:1732-40.
16. Tan EM. Antinuclear antibodies: diagnostic markers for autoimmune diseases and probes for cell biology. Adv Immunol 1989;44:93-151.
17. Winfield JB, Faiferman I, Koffler D. Avidity of anti-dsDNA antibodies in serum and IgG glomerular eluates from patients with systemic lupus erythematosus. J Clin Invest 1977;59:90-9.
18. Bootsma H, Spronk PE, Terborg EJ, Hummel EJ, de Boer G, Limburg PC, et al. The predictive value of fluctuations in IgM and IgG class anti-dsDNA antibodies for relapses in systemic lupus erythematosus. A prospective long term observation. Ann Rheum Dis 1997;56:661-6.
19. Emlen W, Jarusiripipat P, Burdick G. A new ELISA for the detection of double-stranded DNA antibodies. J Immunol Methods 1990;132:91-101.
20. Swaak AJG, Aarden LA, Statius Van Eps LW, Feltkamp TW. Anti-dsDNA and complement profiles as prognostic guides in systemic lupus erythematosus. Arthritis Rheum 1979;22:226-35.
21. Swaak AJG, Groenwold J, Bronsveld W. Predictive value of complement profiles and anti-dsDNA in systemic lupus erythematosus. Ann Rheum Dis 1986;45:359-66.
22. Aarden LA, Lakmaker F, De Groot ER. Immunology of DNA. IV. Quantitative aspects of the Farr assay. J Immunol Methods 1976;11:153-63.
23. Aarden LA, Lakmaker F, Feltkamp TW. Immunology of DNA. II. The effect of size and structure of the antigen on the Farr assay. J Immunol Meth 1976;10:39-48.
24. Emlen W, Pisetsky DS, Taylor RP. Antibodies to DNA. A perspective. Arthritis Rheum 1986;29:1417-126.
25. Miniter MF, Stollar BD, Agnello V. Reassessment of the clinical significance of native DNA antibodies in systemic lupus erythematosus. Arthritis Rheum 1979;22:959-68.
26. Ebling F, Hahn BH. Restricted subpopulations of DNA antibodies in kidneys of mice with systemic lupus: comparison of antibodies in serum and renal elutes. Arthritis Rheum 1980;23:392-403.
27. Vlahakos DV, Foster MH, Adams S, Katz M, Ucci AA, Barrett KJ, et al. Anti-DNA antibodies form immune deposits at distinct glomerula and vascular sites. Kidney Int 1992;41:1690-700.
28. Gilkeson GS, Bernstein K, Rippen AM, Clarke SH, Marion T, Pisetsky DS, et al. The influence of variable region somatic mutations on the specificity and pathogenicity of murine monoclonal anti-DNA antibodies. Clin Immunol Immunopathol 1995;76:59-07.
29. Koffler D, Angello F, Kunkel HG. Polynucleotide immune complexes in serum and glomeruli of patients with systemic lupus erythematosus. Am J Pathol 1974;74:109-24.
30. Krishnan C, Kaplan MH. Immunopathologic studies of systemic lupus erythematosus. II. Antinuclear reaction of gamma-globulin eluted from homogenates and isolated glomeruli of kidneys from patients with lupus nephritis. J Clin Invest 1967;46:569-79.
31. Glassock RJ, Cohen AH, Adler SG, Ward HJ. Secondary glomerular diseases. In: Brenner BM, Rector FC, eds. The kidney. Philadelphia: Saunders, 1991;1 of 2:1280-368.
32. Koffler D, Schur PH, Kunkel HG. Immunological studies concerning the nephritis of systemic lupus erythematosus. J Exp Med 1967;126:607-24.
33. Wallace DJ. Management of lupus erythematosus: recent insights. Curr Opin Rheumatol 2002;14:212-19.
34. Urowitz MA, Gladman DD. In: Wallace DJ, Hahn BH, eds. Dubois lupus erythematosus, 6th edn. Philadelphia: Lippincott, Williams and Wilkins, 2002:1255-174.
35. Petri M, Hopkins. Lupus Cohort 1999 Update. Rheum Dis Clin North Am 2000;26:199-213.
36. Ter Borg EJ, Hummel EJ, Limburg PC, Kallenberg CGM. Measurement of increases in anti-double-stranded DNA antibody levels as a predictor of disease exacerbation in systemic lupus erythematosus: a long-term, prospective study. Arthritis Rheum 1990;33:634-43.
37. Ho A, Magder S, Barr SG, Petri M. Decreases in anti-double-stranded DNA levels are associated with concurrent flares in patients with systemic lupus erythematosus. Arthritis Rheum 2001;44:2342-9.
38. Hahn B, Tsao BP. Antibodies to DNA. In: Wallace DJ, Hahn BH, eds. Dubois lupus erythematosus. 6th ed. Philadelphia: Lippincott, Williams and Wilkins, 2002:195.
39. Tsao BP, Ohnishi K, Cheroutre H, Mitchell B, Teitell M, Mixter P, et al. Failed self-tolerance and autoimmunity in IgG anti-DNA transgenic mice. J Immunol 1992;140:350-38.
40. Tan EM, Cohen AS, Fries JF, Masi T, McShane DJ, Rothfield NF, et al. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1982;25:1271-17.
41. Liang MH, Socher SA, Larson MG, Schur PH. Reliability and validity of six systems for the clinical assessment of disease activity in systemic lupus erythematosus. Arthritis Rheum 1999;42:1309-111.
42. Spertini F, Leimgrube A, Morel B, Khazaeli MB, Yamamoto K, Dayer JM, et al. Idiotypic vaccination with a murine anti-dsDNA antibody: phase I study in patients with nonactive systemic lupus erythematosus. J Rheumatol 1999;26:2602-8.
43. Jouvin MH, Wilson JG, Bourgeois P, Fearon DT, Kazatchkine MD. Decreased expression of C3b receptor (CR1) on erythrocytes of patients with systemic lupus erythematosus contrasts with its normal expression in other systemic diseases and does not correlate with the occurrence of severity of SLE nephritis. Complement 1986;3:88-96.
44. Yen JH, Liu HW, Lin SF, Chen JR, Chen TP. Erythrocyte complement receptor type 1 in patients with systemic lupus erythematosus. J Rheumatol 1989;16:1320-5.
45. McNeeley PA, Iverson GM, Furie RA, Cash JM, Cronin ME, Katz RS, et al. Pre-treatment affinity for LIP 394 influences pharmacodynamic response in lupus patients. Lupus 2001;10:526-32.
46. Alarcón-Segovia D, Tumlin JA, Furie RA, McKoy JD, Cardiel MH, Strand V, et al. LIP 394 for the prevention of renal flare in patients with systemic lupus erythematosus: results from a randomized, double-blind, placebo-controlled study. Arthritis Rheum 2003;48:442-54.
47. Cardiel MH, Tumlin JA, Furie RA, Wallace DJ, Hura C, Strand V, et al. Clinical efficacy results from a RCT of LIP 394 in SLE patients with history or renal disease [abstract]. Arthritis Rheum 2003;48(suppl):S582.
48. Linnik M, Joh T, Strand V, H Cardiel M, Tumlin JA, Furie RA, et al. SLE-patients with sustained reductions in anti-dsDNA antibodies have a reduced risk of renal flare and major SLE flare [abstract]. Arthritis Rheum 2003;48(suppl):S582.