Immunogenicity of Therapeutic Proteins

Handbook of Pharmaceutical Biotechnology

Volumn , Issue , 2006, Pages 815-833

  Hermeling, Suzanne ^a,b   Crommelin, Daan J A ^a   Schellekens, Huub ^a,b   Jiskoot, Wim ^a,c  

^a UTRECHT UNIVERSITY   (Netherlands)

^b UTRECHT UNIVERSITY   (Netherlands)

^c LEIDEN UNIVERSITY   (Netherlands)

Author keywords

Antibody detection; Immune tolerant transgenic mice; Therapeutic protein immunogenicity

Indexed keywords

EID: 79955812055     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1002/9780470117118.ch06d     Document Type: Chapter

References (72)

1. Porter S (2001). Human immune response to recombinant human proteins. J. Pharm. Sci. 90:1-11.
2. Frost H (2005). Antibody-mediated side effects of recombinant proteins. Toxicol. 209:155-160.
3. Casadevall N, Nataf J, Viron B, et al. (2002). Pure red-cell aplasia and antierythropoietin antibodies in patients treated with recombinant erythropoietin. N. Engl. J. Med. 346:469-475.
4. Li J, Yang C, Xia Y, et al. (2001). Thrombocytopenia caused by the development of antibodies to thrombopoietin. Blood. 98:3241-3248.
5. Schellekens H (2005). Factors infl uencing the immunogenicity of therapeutic proteins. Nephrol. Dial. Transplant 20(Suppl 6):vi3-vi9.
6. Chackerian B, Lowy D R, Schiller J T (2001). Conjugation of a self-antigen to papillomavirus-like particles allows for effi cient induction of protective autoantibodies. J. Clin. Invest. 108:415-423.
7. Fehr T, Bachmann M F, Bucher E, et al. (1997). Role of repetitive antigen patterns for induction of antibodies against antibodies. J. Exp. Med. 185:1785-1792.
8. Bachmann M F, Rohrer U H, Kundig T M, et al. (1993). The infl uence of antigen organization on B cell responsiveness. Science. 262:1448-1451.
9. Hermeling S, Crommelin D J A, Schellekens H, et al. (2004). Structure-immunogenicity relationships of therapeutic proteins. Pharm. Res. 21:897-903.
10. Schellekens H (2002). Bioequivalence and the immunogenicity of biopharmaceuticals. Nat. Rev. Drug. Discov. 1:457-462.
11. Chirino A J, Mire-Sluis A (2004). Characterizing biological products and assessing comparability following manufacturing changes. Nat. Biotechnol. 22:1383-1391.
12. Lis H, Sharon N (1993). Protein glycosylation. Structural and functional aspects. Eur. J. Biochem. 218:1-27.
13. Skibeli V, Nissen-Lie G, Torjesen P (2001). Sugar profi ling proves that human serum erythropoietin differs from recombinant human erythropoietin. Blood. 98:3626-3634.
14. Sinclair A M, Elliott S (2005). Glycoengineering: The effect of glycosylation on the properties of therapeutic proteins. J. Pharm. Sci. 94:1626-1635.
15. Runkel L, Meier W, Pepinsky R B, et al. (1998). Structural and functional differences between glycosylated and non-glycosylated forms of human interferon-beta (IFN-beta). Pharm. Res. 15:641-649.
16. Chen M, Liu X, Wang Z, et al. (2005). Modifi cation of plant N-glycans processing: the future of producing therapeutic protein by transgenic plants. Med. Res. Rev. 25:343-360.
17. Chaffee S, Mary A, Stiehm E R, et al. (1992). IgG antibody response to polyethylene glycol-modifi ed adenosine deaminase in patients with adenosine deaminase defi ciency. J. Clin. Invest. 89:1643-1651.
18. Hinds K D, Kim S W (2002). Effects of PEG conjugation on insulin properties. Adv. Drug Deliv. Rev. 54:505-530.
19. Chapman A P (2002). PEGylated antibodies and antibody fragments for improved therapy: A review. Adv. Drug Deliv. Rev. 54:531-545.
20. Chirino A J, Ary M L, Marshall S A (2004). Minimizing the immunogenicity of protein therapeutics. Drug Discov. Today 9:82-90.
21. Caliceti P, Veronese F M (2003). Pharmacokinetic and biodistribution properties of poly(ethylene glycol)-protein conjugates. Adv. Drug Deliv. Rev. 55:1261-1277.
22. Moreland L W, McCabe D P, Caldwell J R, et al. (2000). Phase I/II trial of recombinant methionyl human tumor necrosis factor binding protein PEGylated dimer in patients with active refractory rheumatoid arthritis. J. Rheumatol. 27:601-609.
23. Wadhwa M, Skog A L, Bird C, et al. (1999). Immunogenicity of granulocytemacrophage colony-stimulating factor (GM-CSF) products in patients under going combination therapy with GM-CSF. Clin. Cancer Res. 5:1353-1361.
24. Bertolotto A, Malucchi S, Sala A, et al. (2002). Differential effects of three interferon betas on neutralising antibodies in patients with multiple sclerosis: a follow up study in an independent laboratory. J. Neurol. Neurosurg. Psychiatry 73:148-153.
25. Bertolotto A, Malucchi S, Milano E, et al. (2000). Interferon beta neutralizing antibodies in multiple sclerosis: neutralizing activity and cross-reactivity with three different preparations. Immunopharmacol. 48:95-100.
26. Braun A, Kwee L, Labow M A, et al. (1997). Protein aggregates seem to play a key role among the parameters infl uencing the antigenicity of interferon alpha (IFN-alpha) in normal and transgenic mice. Pharm. Res. 14:1472-1478.
27. Moore W V, Leppert P (1980). Role of aggregated human growth hormone (hGH) in development of antibodies to hGH. J. Clin. Endocrinol. Metab. 51:691-697.
28. Wang W (2005). Protein aggregation and its inhibition in biopharmaceutics. Int. J. Pharm. 289:1-30.
29. Hermeling S (2005). Structural Aspects of the Immunogenicity of Therapeutic Proteins; Transgenic Animals as Predictors for Breaking Immune Tolerance. Utrecht University, Utrecht, The Netherlands, pp. 208.
30. Prescott R, Nakai H, Saenko E L, et al. (1997). The inhibitor antibody response is more complex in hemophilia A patients than in most nonhemophiliacs with factor VIII autoantibodies. Recombinate and Kogenate Study Groups. Blood. 89:3663-3671.
31. Gilles J G, Jacquemin M G, Saint-Remy J M (1997). Factor VIII inhibitors. Thromb. Haemost. 78:641-646.
32. Schellekens H (2005). Immunologic mechanisms of EPO-associated pure red cell aplasia. Best Pract. Res. Clin. Haematol. 18:473-480.
33. Palleroni A V, Aglione A, Labow M, et al. (1997). Interferon immunogenicity:Preclinical evaluation of interferon-alpha 2a. J. Interferon Cytokine Res. 17(Suppl 1):S23-27.
34. Ryff J C (1997). Clinical investigation of the immunogenicity of interferon-alpha 2a. J. Interferon Cytokine Res. 17(Suppl 1):S29-33.
35. Mire-Sluis A R, Barrett Y C, Devanarayan V, et al. (2004). Recommendations for the design and optimization of immunoassays used in the detection of host antibodies against biotechnology products. J. Immunol. Methods. 289:1-16.
36. Wadhwa M, Bird C, Dilger P, et al. (2003). Strategies for detection, measurement and characterization of unwanted antibodies induced by therapeutic biologicals. J. Immunol. Methods. 278:1-17.
37. Kersten G F, Westdijk J (2005). Immunoassays. In W Jiskoot and D J A Crommelin (eds.), Methods for Structural Analysis of Protein Pharmaeuticals, Vol. III, Biotechnology:Pharmaceutical Aspects, AAPS Press, Arlington, V.A., pp. 501-526.
38. Brickelmaier M, Hochman P S, Baciu R, et al. (1999). ELISA methods for the analysis of antibody responses induced in multiple sclerosis patients treated with recombinant interferon-beta. J. Immunol. Methods. 227:121-135.
39. Schellekens H (2002). Immunogenicity of therapeutic proteins: Clinical implications and future prospects. Clin. Ther. 24:1720-1740.
40. Bugelski P J, Treacy G (2004). Predictive power of preclinical studies in animals for the immunogenicity of recombinant therapeutic proteins in humans. Curr. Opin. Mol. Ther. 6:10-16.
41. Rosenberg A S, Worobec A (2005). A risk-based approach to immunogenicity concerns of therapeutic protein products, Part 3: Effects of manufacturing changes in imuunogenicity and the utility of animal immunogenicity studies. Biopharm. Int. Jan. 1, 2005:1-3.
42. Wierda D, Smith H W, Zwickl C M (2001). Immunogenicity of biopharmaceuticals in laboratory animals. Toxicol. 158:71-74.
43. Simioni P U, Fernandes L G, Gabriel D L, et al. (2004). Induction of systemic tolerance in normal but not in transgenic mice through continuous feeding of ovalbumin. Scand. J. Immunol. 60:257-266.
44. Zhang J, Xu L, Haskins M E, et al. (2004). Neonatal gene transfer with a retroviral vector results in tolerance to human factor IX in mice and dogs. Blood. 103:143-151.
45. Ottesen J L, Nilsson P, Jami J, et al. (1994). The potential immunogenicity of human insulin and insulin analogues evaluated in a transgenic mouse model. Diabetologia. 37:1178-1185.
46. Stewart T A, Hollingshead P G, Pitts S L, et al. (1989). Transgenic mice as a model to test the immunogenicity of proteins altered by site-specifi c mutagenesis. Mol. Biol. Med. 6:275-281.
47. Hermeling S, Jiskoot W, Crommelin D J A, et al. (2005). Development of a transgenic mouse model immune tolerant for human interferon beta. Pharm. Res. 22:847-851.
48. Yeung V P, Chang J, Miller J, et al. (2004). Elimination of an immunodominant CD4+ T cell epitope in human IFN-beta does not result in an in vivo response directed at the subdominant epitope. J. Immunol. 172:6658-6665.
49. Saha S, Bhasin M, Raghava G P (2005). Bcipep: A database of B-cell epitopes. BMC Genomics. 6:79.
50. Koren E, Zuckerman L A, Mire-Sluis A R (2002). Immune responses to therapeutic proteins in humans-clinical signifi cance, assessment and prediction. Curr. Pharm. Biotechnol. 3:349-360.
51. Antonelli G (1997). In vivo development of antibody to interferons: an update to 1996. J. Interferon Cytokine Res. 17(Suppl 1):S39-46.
52. Thorpe R, Swanson S J (2005). Current methods for detecting antibodies against erythropoietin and other recombinant proteins. Clin. Diagn. Lab Immunol. 12:28-39.
53. Quesada J R, Rios A, Swanson D, et al. (1985). Antitumor activity of recombinantderived interferon alpha in metastatic renal cell carcinoma. J. Clin. Oncol. 3:1522-1528.
54. Rosenberg A S, Worobec A (2004). A risk-based approach to immunogenicity concerns of therapeutic protein products, Part 1: Considering consequences of the immune response to a protein. Biopharm. Int. Nov. 1, 2004:1-4.
55. Rosenberg A S, Worobec A (2004). A risk-based approach to immunogenicity concerns of therapeutic protein products, Part 2: Considering host-specifi c and product-specifi c factors impacting immunogenicity. Biopharm. Int. Dec. 1, 2004:1-7.
56. Prabhakar S S, Muhlfelder T (1997). Antibodies to recombinant human erythropoietin causing pure red cell aplasia. Clin. Nephrol. 47:331-335.
57. Hermeling S, Schellekens H, Crommelin D J A, et al. (2003). Micelle-associated protein in epoetin formulations: A risk factor for immunogenicity? Pharm. Res. 20:1903-1907.
58. Sharma B, Bader F, Templeman T, et al. (2004). Technical investigations into the cause of the increased incidence of antibody-mediated pure-red cell aplasia associated with Eprex®. Eur. J. Hosp. Pharm. 5:86-91.
59. Antonelli G, Dianzani F (1999). Development of antibodies to interferon beta in patients: technical and biological aspects. Eur. Cytokine Netw. 10:413-422.
60. Mayorga C, Luque G, Romero F, et al. (1999). Antibodies to commercially available interferon-beta molecules in multiple sclerosis patients treated with natural interferonbeta. Int. Arch. Allergy Immunol. 118:368-371.
61. Malucchi S, Sala A, Gilli F, et al. (2004). Neutralizing antibodies reduce the effi cacy of betaIFN during treatment of multiple sclerosis. Neurol. 62:2031-2037.
62. Sorensen P S, Ross C, Clemmesen K M, et al. (2003). Clinical importance of neutralising antibodies against interferon beta in patients with relapsing-remitting multiple sclerosis. Lancet. 362:1184-1191.
63. Pachner A R (2003). Anti-IFNbeta antibodies in IFNbeta treated MS patients. Neurol. 61:S1-S5.
64. Bertolotto A (2004). Neutralizing antibodies to interferon beta: implications for the management of multiple sclerosis. Curr. Opin. Neurol. 17:241-246.
65. Cook S D, Quinless J R, Jotkowitz A, et al. (2001). Serum IFN neutralizing antibodies and neopterin levels in a cross-section of MS patients. Neurol. 57:1080-1084.
66. Pfeffer L M, Dinarello C A, Herberman R B, et al. (1998). Biological properties of recombinant alpha-interferons: 40th anniversary of the discovery of inter ferons. Cancer Res. 58:2489-2499.
67. Adolf G R, Kalsner I, Ahorn H, et al. (1991). Natural human interferon-alpha 2 is Oglycosylated. Biochem. J. 276 (Pt 2):511-518.
68. Antonelli G, Currenti M, Turriziani O, et al. (1991). Neutralizing antibodies to interferon-alpha: relative frequency in patients treated with different interferon preparations. J. Infect. Dis. 163:882-885.
69. Intermune. Infergen (Interferon alfacon-1). Available: http://www.infergen.com/pdf/infergen_pi.pdf. Accessed July 26, 2005.
70. Tong M J, Reddy K R, Lee W M, et al. (1997). Treatment of chronic hepatitis C with consensus interferon: A multicenter, randomized, controlled trial. Consensus Interferon Study Group. Hepatol. 26:747-754.
71. Hermeling S, Aranha L, Damen J M A, et al. (2005). Structural characterization and immunogenicity in wildtype and immune tolerant mice of degraded recombinant human interferon alpha2b. Pharm. Res. In Press.
72. Hochuli E (1997). Interferon immunogenicity: technical evaluation of interferon-alpha 2a. J. Interferon Cytokine Res. 17(Suppl 1):S15-21.