Human Immune Response to Recombinant Human Proteins

Porter, Seth

doi:10.1002/1520-6017(200101)90:1<1::aid-jps1>3.0.co;2-k

Cited by 162 publications

(51 citation statements)

References 64 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…4 However, the clinical impact of antibodies ranges from no significant effect 23 to almost complete failure of therapy. Non-tolerized serum taken from a patient (patient 3) on ERT before HSCT with high titer antibodies is compared to tolerized serum taken from the same patient a year after HSCT (with no antibodies) which shows no significant inhibition.…”

Section: Discussionmentioning

confidence: 99%

“…3 The clinical importance of antibodies in ERT-treated patients is uncertain but the existence of an allo-immune response to infused exogenous enzyme and recombinant human proteins is well described. [4][5] In early clinical trials the reported incidence of IDUA-specific antibodies was low (40%) and there was no evidence of immunoprecipitation of enzyme or inhibition of catalytic activity. 6 Subsequently, a prospective, open-label, multinational study revealed a suboptimal biomarker response in the presence of high antibody titers (> 1:10,000) when compared to that in patients with no alloimmune response.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Hematopoietic stem cell transplantation improves the high incidence of neutralizing allo-antibodies observed in Hurler's syndrome after pharmacological enzyme replacement therapy

Saif¹,

Bigger²,

Brookes³

et al. 2012

Haematologica

View full text Add to dashboard Cite

BackgroundMucopolysaccharidosis type I is caused by deficiency of a-L-iduronidase. Currently available treatment options include an allogeneic hematopoietic stem cell transplant and enzyme replacement therapy. Exogenous enzyme therapy appears promising but the benefits may be attenuated, at least in some patients, by the development of an immune response to the delivered enzyme. The incidence and impact of allo-immune responses in these patients remain unknown. Design and MethodsWe developed an immunoglobulin G enzyme-linked immunosorbent assay as well as in vitro catalytic enzyme inhibition and cellular uptake inhibition assays and quantified enzyme inhibition by allo-antibodies. We determined the impact of these antibodies in eight patients who received enzyme therapy before and during hematopoietic stem cell transplantation. In addition, 20 patients who had previously received an allogeneic stem cell transplant were tested to evaluate this treatment as an immune tolerance induction mechanism. ResultsHigh titer immune responses were seen in 87.5% (7/8) patients following exposure to a-Liduronidase. These patients exhibited catalytic enzyme inhibition (5/8), uptake inhibition of catalytically active enzyme (6/8) or both (4/8). High antibody titers generally preceded elevation of previously described biomarkers of disease progression. The median time to development of immune tolerance was 101 days (range, 26-137) after transplantation. All 20 patients, including those with mixed chimerism (22%), tested 1 year after transplantation were tolerized despite normal enzyme levels. ConclusionsWe found a high incidence of neutralizing antibodies in patients with mucopolysaccharidosis type I treated with enzyme replacement therapy. We also found that allogeneic hematopoietic stem cell transplantation was an effective and rapid immune tolerance induction strategy. © F e r r a t a S t o r t i F o u n d a t i o n © F e r r a t a S t o r t i F o u n d a t i o n

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Hematopoietic stem cell transplantation improves the high incidence of neutralizing allo-antibodies observed in Hurler's syndrome after pharmacological enzyme replacement therapy

Saif¹,

Bigger²,

Brookes³

et al. 2012

Haematologica

View full text Add to dashboard Cite

show abstract

“…Immune responses directed against biological therapeutics have been recognized as a major concern limiting the long-term use of these medicines (Porter, 2001;Koren et al, 2002;Stein, 2002). Such immune responses are often benign, but in some instances, they can have undesirable effect(s), ranging from mild to severe adverse anaphylactoid reactions or in some cases, reduced clinical efficacy, or sometimes even worse, severe clinical consequences in recipients of such therapies (Steis et al, 1988;Rosenberg et al, 1999;Wadhwa et al, 1999;Hjelm Skog et al;2001;Li et al, 2001;Casadevall et al, 2002;Saint-Remy, 2002;Baert et al, 2003;Bertolotto, 2004;Francis et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Strategies and Assays for the Assessment of Unwanted Immunogenicity

Wadhwa¹,

Thorpe²

2006

Journal of Immunotoxicology

View full text Add to dashboard Cite

The assessment of unwanted immunogenicity associated with biological products continues to be a major issue for the biotechnology industry. Monitoring of unwanted immunogenicity during the development of the product from pre-clinical stage through clinical trials is now a regulatory expectation with extended post-marketing commitments required for at least some of these products. Prospective planning of immunogenicity studies incorporating appropriately devised strategies is critical if valid conclusions concerning the immunogenicity profile of a product are to be derived. An important consideration of such studies is the selection of optimized, rigorously validated and standardized methodologies for detection and characterization of antibodies with emphasis on desired assay design, assay controls, and performance criteria. Binding assays with different formats and detection systems, radioimmunoprecipitation assays or surface plasmon resonance procedures are often used as the basis for a screening assay. For assessing the neutralizing capacity of the antibodies, however, a neutralization assay is an absolute requirement. Therefore, a panel of methods is usually necessary for a detailed understanding of the type(s) of antibodies induced against a therapeutic product. This manuscript considers briefly the benefits and limitations of the different techniques available for antibody detection and characterization. A strategy that can be adopted for the assessment of unwanted immunogenicity of therapeutic products is also suggested.

show abstract

“…Although the occurrence of antibodies (Abs) towards recombinant human proteins is not uncommon, immune reactions have not been a major impediment to their therapeutic use [35]. First, Abs production can be transient.…”

Section: Immunogenicity Of Recombinant Therapeuticsmentioning

confidence: 99%

Biosimilar epoetins and other “follow‐on” biologics: Update on the European experiences

Jelkmann¹

2010

American J Hematol

View full text Add to dashboard Cite

After the patents of biopharmaceuticals have expired, based on specific regulatory approval pathways copied products (“biosimilars” or “follow‐on biologics”) have been launched in the EU. This article summarizes experiences with hematopoietic medicines, namely the epoetins (two biosimilars traded under five different brand names) and the filgrastims (two biosimilars, six brand names). Physicians and pharmacists should be familiar with the legal and pharmacological specialities of biosimilars: The production process can differ from that of the original, clinical indications can be extrapolated, glycoproteins contain varying isoforms, the formulation may differ from the original, and biopharmaceuticals are potentially immunogenic. Only on proof of quality, efficacy and safety, biosimilars are a viable option because of their lower costs. Am. J. Hematol. 2010. © 2010 Wiley‐Liss, Inc.

show abstract

Human Immune Response to Recombinant Human Proteins

Cited by 162 publications

References 64 publications

Hematopoietic stem cell transplantation improves the high incidence of neutralizing allo-antibodies observed in Hurler's syndrome after pharmacological enzyme replacement therapy

Hematopoietic stem cell transplantation improves the high incidence of neutralizing allo-antibodies observed in Hurler's syndrome after pharmacological enzyme replacement therapy

Strategies and Assays for the Assessment of Unwanted Immunogenicity

Biosimilar epoetins and other “follow‐on” biologics: Update on the European experiences

Contact Info

Product

Resources

About