Student or educator? Sign up with your school email and get 6 months of Pro free.
Cited by 556

The DOI matches its Crossref record.

Immunogenicity of therapeutic proteins: Clinical implications and future prospects

Schellekens, Huub·2002·Clinical Therapeutics

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1016/s0149-2918(02)80075-3

Cites

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

No references could be resolved yet.

Research works printed but not linked: 84

  1. Myhr, 2000, Neutralizing antibodies to interferon (IFN) alpha-2a and IFN beta-1a or IFN beta-1b in MS are not cross-reactive, Neurology, 55, 1569, 10.1212/WNL.55.10.1569 · doi:10.1212/wnl.55.10.1569
  2. Oberg, 1989, Treatment of malignant carcinoid tumors with recombinant interferon alfa-2b: Development of neutralizing interferon antibodies and possible loss of antitumor activity, J Natl Cancer Inst, 81, 531, 10.1093/jnci/81.7.531 · doi:10.1093/jnci/81.7.531
  3. Olsen, 2001, Pivotal phase III trial of two dose levels of denileukin diftitox for the treatment of cutaneous T-cell lymphoma, J Clin Oncol, 19, 376, 10.1200/JCO.2001.19.2.376 · DOI · Paper page
  4. Gelfand, 2001, Antibody-directed therapy: Past, present, and future, J Allergy Clin Immunol, 108, S111, 10.1067/mai.2001.117824 · doi:10.1067/mai.2001.117824
  5. Hurter, 1970, Activity and binding capacity of bovine and porcine insulin binding antibodies in childhood diabetes [in German], Monatsschr Kinderheilkd, 118, 250
  6. Rosenschein, 1991, Streptokinase immunogenicity in thrombolytic therapy for acute myocardial infarction, Isr J Med Sci, 27, 541
  7. Vanderschueren, 1994, On the immunogenicity of recombinant staphylokinase in patients and in animal models, Thromb Haemost, 72, 297, 10.1055/s-0038-1648856 · doi:10.1055/s-0038-1648856
  8. Schellekens, 2002, Bioequivalence and the immunogenicity of biopharmaceuticals, Nat Rev Drug Discov, 1, 457, 10.1038/nrd818 · DOI · Paper page
  9. Ryff, 2002, Immunogenicity of rDNA-derived pharmaceuticals, Trends Pharmacol Sci, 23, 254, 10.1016/S0165-6147(02)02024-2 · DOI
  10. Porter, 2001, Human immune response to recombinant human proteins, J Pharm Sci, 90, 1, 10.1002/1520-6017(200101)90:1<1::AID-JPS1>3.0.CO;2-K · DOI
  11. Ryff, 1997, Clinical investigation of the immunogenicity of interferon-alpha 2a, J Interferon Cytokine Res, 17, S29
  12. Perini, 2001, Interferon-beta (INF-beta) antibodies in interferon-beta1a- and interferon-beta1b-treated multiple sclerosis patients. Prevalence, kinetics, cross-reactivity, and factors enhancing interferon-beta immunogenicity in vivo, Eur Cytokine Netw, 12, 56
  13. Gribben, 1990, Development of antibodies to unprotected glycosylation sites on recombinant human GM-CSF, Lancet, 335, 434, 10.1016/0140-6736(90)90665-R · DOI · Paper page
  14. Antonelli, 1996, Antibodies to interferon (IFN) in hepatitis C patients relapsing while continuing recombinant IFN-alpha2 therapy, Clin Exp Immunol, 104, 384, 10.1046/j.1365-2249.1996.43747.x · doi:10.1046/j.1365-2249.1996.43747.x
  15. Figlin, 1988, Anti-interferon antibodies: A perspective, Semin Hematol, 25, 9
  16. Grauer, 1995, Clinical significance of antibodies against calcitonin, Exp Clin Endocrinol Diabetes, 103, 345, 10.1055/s-0029-1211376 · DOI · Paper page
  17. Jacquemin, 1998, Factor VIII immunogenicity, Haemophilia, 4, 552, 10.1046/j.1365-2516.1998.440552.x · doi:10.1046/j.1365-2516.1998.440552.x
  18. Giannelli, 1994, Biological and clinical significance of neutralizing and binding antibodies to interferon-alpha (IFN-alpha) during therapy for chronic hepatitis C, Clin Exp Immunol, 97, 4, 10.1111/j.1365-2249.1994.tb06571.x · doi:10.1111/j.1365-2249.1994.tb06571.x
  19. McSweeney, 1993, Recombinant interferon alfa 2a in the treatment of patients with early stage B chronic lymphocytic leukaemia, Br J Haematol, 85, 77, 10.1111/j.1365-2141.1993.tb08648.x · doi:10.1111/j.1365-2141.1993.tb08648.x
  20. Lok, 1990, Interferon antibodies may negate the antiviral effects of recombinant alpha-interferon treatment in patients with chronic hepatitis B virus infection, Hepatology, 12, 1266, 10.1002/hep.1840120603 · doi:10.1002/hep.1840120603
  21. Fossa, 1992, Recombinant interferon alpha-2A combined with prednisone in metastatic renal-cell carcinoma: Treatment results, serum interferon levels and the development of antibodies, Int J Cancer, 50, 868, 10.1002/ijc.2910500606 · DOI
  22. Bonetti, 1994, Interferon antibodies in patients with chronic hepatitis C virus infection treated with recombinant interferon alpha-2 alpha, J Hepatol, 20, 416, 10.1016/S0168-8278(94)80018-9 · DOI
  23. Prümmer, 1997, Treatment-induced antibodies to interleukin-2, Biotherapy, 10, 15, 10.1007/BF02678213 · DOI
  24. Blumenfeld, 1988, Gonadotropin-releasing hormone (GnRH) antibodies formation in hypogonadotropic azoospermic men treated with pulsatile GnRH—diagnosis and possible alternative treatment, Fertil Steril, 50, 622, 10.1016/S0015-0282(16)60195-4 · DOI
  25. Claustrat, 1983, Development of anti-human chorionic gonadotropin antibodies in patients with hypogonadotropic hypogonadism. A study of four patients, J Clin Endocrinol Metab, 57, 1041, 10.1210/jcem-57-5-1041 · doi:10.1210/jcem-57-5-1041
  26. Ragnhammar, 1996, Neutralising antibodies to granulocyte-macrophage colony stimulating factor (GM-CSF) in carcinoma patients following GM-CSF combination therapy, Med Oncol, 13, 161, 10.1007/BF02990843 · doi:10.1007/bf02990843
  27. Venekamp, 1985, Immunogenicity of bovine, porcine and semisynthetic human insulin, Neth J Med, 28, 57
  28. Schernthaner, 1993, Immunogenicity and allergenic potential of animal and human insulins, Diabetes Care, 16, 155, 10.2337/diacare.16.3.155 · DOI · Paper page
  29. Fineberg, 1983, Immunogenicity of recombinant DNA human insulin, Diabetologia, 25, 465, 10.1007/BF00284452 · DOI · Paper page
  30. Casadevall, 2002, Pure red-cell aplasia and antierythropoietin antibodies in patients treated with recombinant erythropoietin, N Engl J Med, 346, 469, 10.1056/NEJMoa011931 · DOI · Paper page
  31. Casadevall, 2002, N Engl J Med, 346, 1585, 10.1056/NEJMoa011931 · DOI · Paper page
  32. Briet, 2001, The incidence of inhibitors in hemophilia A and the induction of immune tolerance, Adv Exp Med Biol, 489, 89, 10.1007/978-1-4615-1277-6_8 · DOI
  33. Eisenberg, 1997, Safety of repeated intermittent courses of aerosolized recombinant human deoxyribonuclease in patients with cystic fibrosis, J Pediatr, 131, 118, 10.1016/S0022-3476(97)70134-3 · DOI
  34. Zang, 2000, Immunoregulation and blocking antibodies induced by interferon beta treatment in MS, Neurology, 55, 397, 10.1212/WNL.55.3.397 · DOI
  35. Bukowski, 1996, Phase I trial of subcutaneous interleukin 3 in patients with refractory malignancy: Hematological, immunological, and pharmacodynamic findings, Clin Cancer Res, 2, 347
  36. Miller, 1999, Abrogation of the hematological and biological activities of the interleukin-3/granulocyte-macrophage colony-stimulating factor fusion protein PIXY321 by neutralizing anti-PIXY321 antibodies in cancer patients receiving high-dose carboplatin, Blood, 93, 3250, 10.1182/blood.V93.10.3250.410k35_3250_3258 · DOI
  37. Ragnhammar, 1994, Induction of anti-recombinant human granulocyte-macrophage colony-stimulating factor (Escherichia coli-derived) antibodies and clinical effects in nonimmuno-compromised patients, Blood, 84, 4078, 10.1182/blood.V84.12.4078.bloodjournal84124078 · doi:10.1182/blood.v84.12.4078.bloodjournal84124078
  38. Laricchia-Robbio, 1997, Naturally occurring and therapy-induced antibodies to human granulocyte colony-stimulating factor (G-CSF) in human serum, J Cell Physiol, 173, 219, 10.1002/(SICI)1097-4652(199711)173:2<219::AID-JCP25>3.0.CO;2-9 · doi:10.1002/(sici)1097-4652(199711)173:2<219::aid-jcp25>3.0.co;2-9
  39. Husson, 1992, Phase I study of continuous-infusion soluble CD4 as a single agent and in combination with oral dideoxyinosine therapy in children with symptomatic human immunodeficiency virus infection, J Pediatr, 121, 627, 10.1016/S0022-3476(05)81161-8 · doi:10.1016/s0022-3476(05)81161-8
  40. 1999, TNF neutralization in MS: Results of a randomized, placebo-controlled multicenter study, Neurology, 53, 457, 10.1212/WNL.53.3.457 · DOI · Paper page
  41. Gershon, 2002, Pure red-cell aplasia and recombinant erythropoietin, N Engl J Med, 346, 1584, 10.1056/NEJM200205163462015 · DOI
  42. Cleland, 1993, The development of stable protein formulations: A close look at protein aggregation, deamidation, and oxidation, Crit Rev Ther Drug Carrier Syst, 10, 307
  43. Fakharzadeh, 2000, Correlation between factor VIII genotype and inhibitor development in hemophilia A, Semin Thromb Hemost, 26, 167, 10.1055/s-2000-9819 · DOI
  44. Prescott, 1997, The inhibitor antibody response is more complex in hemophilia A patients than in most nonhemophiliacs with factor VIII autoantibodies, Blood, 89, 3663, 10.1182/blood.V89.10.3663 · DOI · Paper page
  45. Reeves, 1984, HLA phenotype and insulin antibody production, Clin Exp Immunol, 57, 443
  46. Van Haeften, 1989, Clinical significance of insulin antibodies in insulin-treated diabetic patients, Diabetes Care, 12, 641, 10.2337/diacare.12.9.641 · doi:10.2337/diacare.12.9.641
  47. Palleroni, 1997, Interferon immunogenicity: Preclinical evaluation of interferon-alpha 2a, J Interferon Cytokine Res, 17, S23
  48. Antonelli, 1999, Development of antibodies to interferon beta in patients: Technical and biological aspects, Eur Cytokine Netw, 10, 413
  49. Chance, 1976, The immunogenicity of insulin preparations, Acta Endocrinol Suppl (Copenh), 205, 185
  50. Lawley, 2000, T-cell recognition of discrete regions of the thrombolytic drug streptokinase, Clin Sci (Lond), 99, 239, 10.1042/CS19990354 · doi:10.1042/cs19990354
  51. Chang, 2000, Towards a quantitative model of immunogenicity: Counting pathways in sequence space, J Theor Biol, 206, 255, 10.1006/jtbi.2000.2122 · DOI
  52. Fierlbeck, 1994, Neutralizing interferon beta antibodies in melanoma patients treated with recombinant and natural interferon beta, Cancer Immunol Immunother, 39, 263, 10.1007/BF01525990 · doi:10.1007/bf01525990
  53. Preece, 1993, Human pituitary growth hormone and Creutzfeldt-Jakob disease, Horm Res, 39, 95, 10.1159/000182704 · doi:10.1159/000182704
  54. Peces, 1996, Antibodies against recombinant human erythropoietin in a patient with erythropoietin-resistant anemia, N Engl J Med, 335, 523, 10.1056/NEJM199608153350717 · doi:10.1056/nejm199608153350717
  55. Kontsek, 1999, Immunogenicity of interferon-alpha 2 in therapy: Structural and physiological aspects, Acta Virol, 43, 63
  56. Melian, 2001, Interferon alfacon-1: A review of its pharmacology and therapeutic efficacy in the treatment of chronic hepatitis C, Drugs, 61, 1661, 10.2165/00003495-200161110-00009 · doi:10.2165/00003495-200161110-00009
  57. Girard, 1986, Clinical experience with Somatonorm, Acta Paediatr Scand Suppl, 325, 29, 10.1111/j.1651-2227.1986.tb10360.x · doi:10.1111/j.1651-2227.1986.tb10360.x
  58. Ross, 2000, Immunogenicity of interferon-beta in multiple sclerosis patients: Influence of preparation, dosage, dose frequency, and route of administration, Ann Neurol, 48, 706, 10.1002/1531-8249(200011)48:5<706::AID-ANA3>3.0.CO;2-V · DOI
  59. Levy, 1988, Formation of neutralizing antibodies during intranasal synthetic salmon calcitonin treatment of Paget's disease, J Clin Endocrinol Metab, 67, 541, 10.1210/jcem-67-3-541 · DOI
  60. Cross, 1998, Antibodies to beta-interferons in multiple sclerosis: Can we neutralize the controversy?, Neurology, 50, 1206, 10.1212/WNL.50.5.1206 · doi:10.1212/wnl.50.5.1206
  61. Hochuli, 1997, Interferon immunogenicity: Technical evaluation of interferon-alpha 2a, J Interferon Cytokine Res, 17, S15
  62. Rosendaal, 1993, A sudden increase in factor VIII inhibitor development in multi-transfused hemophilia A patients in The Netherlands, Blood, 81, 2180, 10.1182/blood.V81.8.2180.2180 · DOI · Paper page
  63. Casato, 1991, Long-term results of therapy with interferon-alpha for type II essential mixed cryoglobulinemia, Blood, 78, 3142, 10.1182/blood.V78.12.3142.3142 · doi:10.1182/blood.v78.12.3142.3142
  64. von Wussow, 1991, Effective natural interferon-alpha therapy in recombinant interferon-alpha-resistant patients with hairy cell leukemia, Blood, 78, 38, 10.1182/blood.V78.1.38.38 · doi:10.1182/blood.v78.1.38.38
  65. Roffi, 1995, Breakthrough during recombinant interferon alfa therapy in patients with chronic hepatitis C virus infection: Prevalence, etiology, and management, Hepatology, 21, 645, 10.1002/hep.1840210307 · doi:10.1002/hep.1840210307
  66. von Wussow, 1988, Leucocyte-derived interferon-alpha in patients with antibodies to recombinant IFN-alpha 2b, Lancet, 1, 882, 10.1016/S0140-6736(88)91628-5 · doi:10.1016/s0140-6736(88)91628-5
  67. Khan, 1998, Neutralizing antibodies to interferon beta-1a and interferon beta-1b in MS patients are cross-reactive, Neurology, 51, 1698, 10.1212/WNL.51.6.1698 · DOI
  68. Bertolotto, 2000, Interferon beta neutralizing antibodies in multiple sclerosis: Neutralizing activity and cross-reactivity with three different preparations, Immunopharmacology, 48, 95, 10.1016/S0162-3109(00)00182-X · DOI
  69. Mariani, 1994, Immune tolerance in hemophilia—principal results from the International Registry. Report of the factor VIII and IX Subcommittee, Thromb Haemost, 72, 155, 10.1055/s-0038-1648828 · doi:10.1055/s-0038-1648828
  70. Adair, 2002, The immunogenicity of therapeutic proteins, BioPharm, 15, 30
  71. Wierda, 2001, Immunogenicity of biopharmaceuticals in laboratory animals, Toxicology, 158, 71, 10.1016/S0300-483X(00)00410-8 · DOI
  72. Zwickl, 1991, Comparison of the immunogenicity of recombinant and pituitary human growth hormone in rhesus monkeys, Fundam Appl Toxicol, 16, 275, 10.1016/0272-0590(91)90112-H · DOI
  73. Stewart, 1989, Transgenic mice as a model to test the immunogenicity of proteins altered by site-specific mutagenesis, Mol Biol Med, 6, 275
  74. Ottesen, 1994, The potential immunogenicity of human insulin and insulin analogues evaluated in a transgenic mouse model, Diabetologia, 37, 1178, 10.1007/BF00399790 · DOI
  75. Shiffman, 2001, Pegylated interferons: What role will they play in the treatment of chronic hepatitis C?, Curr Gastroenterol Rep, 3, 30, 10.1007/s11894-001-0038-z · DOI
  76. Perry, 2002, Spotlight on peginterferon-alpha-2a (40KD) in chronic hepatitis C, BioDrugs, 16, 213, 10.2165/00063030-200216030-00006 · doi:10.2165/00063030-200216030-00006
  77. Wang, 2002, Structural and biological characterization of pegylated recombinant interferon alpha-2b and its therapeutic implications, Adv Drug Deliv Rev, 54, 547, 10.1016/S0169-409X(02)00027-3 · DOI · Paper page
  78. Wan, 2002, An enzyme-linked immunosorbent assay for host cell protein contaminants in recombinant PEGylated staphylokinase mutant SY161, J Pharm Biomed Anal, 28, 953, 10.1016/S0731-7085(01)00712-9 · doi:10.1016/s0731-7085(01)00712-9
  79. Kolkman, 2001, Directed evolution of proteins by exon shuffling, Nat Biotechnol, 19, 423, 10.1038/88084 · DOI · Paper page
  80. Pavlinkova, 2001, Effects of humanization and gene shuffling on immunogenicity and antigen binding of anti-TAG-72 single-chain Fvs, Int J Cancer, 94, 717, 10.1002/ijc.1523 · DOI
  81. Klingbeil, 1999, Pharmacology and safety assessment of humanized monoclonal antibodies for therapeutic use, Toxicol Pathol, 27, 1, 10.1177/019262339902700101 · DOI
  82. Baselga, 1999, Phase II study of weekly intravenous trastuzumab (Herceptin) in patients with HER2/neu-overexpressing metastatic breast cancer, Semin Oncol, 26, 78
  83. Milgrom, 1999, Treatment of allergic asthma with monoclonal anti-IgE antibody, N Engl J Med, 341, 1966, 10.1056/NEJM199912233412603 · DOI · Paper page
  84. Matteson, 1995, Treatment of active refractory rheumatoid arthritis with humanized monoclonal antibody CAMPATH-1H administered by daily subcutaneous injection, Arthritis Rheum, 38, 1187, 10.1002/art.1780380903 · doi:10.1002/art.1780380903

Cited by

See all 556

Metadata

Authors
Schellekens, H.
Venue
Clinical Therapeutics
Publisher
Elsevier BV
Published
2002-11
Volume
24
Issue
11
Pages
1720-1740
ISSN
0149-2918 (ISSN-L)
OpenAlex
W2024304683
Cited by
556
References
0
FWCI
4.82
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

How to cite

Cite CoChat for the checks on this page, and the paper for its own findings.

This page
CoChat. (2026). Citation check: Immunogenicity of therapeutic proteins: Clinical implications and future prospects. https://app.cochat.ai/papers/10.1016/s0149-2918(02)80075-3
The paper
Schellekens, H. (2002). Immunogenicity of therapeutic proteins: Clinical implications and future prospects. Clinical Therapeutics. https://doi.org/10.1016/s0149-2918(02)80075-3

Data sources

Bibliographic data: Semantic Scholar, OpenAlex, Crossref.

Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.