Immunogenicity of therapeutic proteins

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Immunogenicity of therapeutic proteins.

A year ago Nicole Casadevall of the Hotel-Dieu in Paris and her colleagues published their first 13 cases of pure red-cell aplasia (PRCA) associated with the use of erythropoietin (Epo) in patients with chronic renal failure [1]. As of November 2002, the number of antibody-mediated reported cases in Europe, Canada and Australia has increased to more than 175. The most likely explanation for thi...

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Immunogenicity of therapeutic proteins: Influence of aggregation

The elicitation of anti-drug antibodies (ADA) against biotherapeutics can have detrimental effects on drug safety, efficacy, and pharmacokinetics. The immunogenicity of biotherapeutics is, therefore, an important issue. There is evidence that protein aggregation can result in enhanced immunogenicity; however, the precise immunological and biochemical mechanisms responsible are poorly defined. I...

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Factors influencing the immunogenicity of therapeutic proteins.

Several diseases and disorders are treatable with therapeutic proteins, but some of these products may induce an immune response, especially when administered as multiple doses over prolonged periods. Antibodies are created by classical immune reactions or by the breakdown of immune tolerance; the latter is characteristic of human homologue products. Many factors influence the immunogenicity of...

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Rationally engineered therapeutic proteins with reduced immunogenicity.

Chronic administration of protein therapeutics may elicit unacceptable immune responses to the specific protein. Our hypothesis is that the immunogenicity of protein drugs can be ascribed to a few immunodominant helper T lymphocyte (HTL) epitopes, and that reducing the MHC binding affinity of these HTL epitopes contained within these proteins can generate drugs with lower immunogenicity. To tes...

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Prediction of immunogenicity for therapeutic proteins: state of the art.

Immunogenicity is a significant problem associated with protein therapeutics, but can be predicted in advance by in silico, in vitro, and in vivo tools, which can identifiy sequences within the therapeutic protein that, when processed by T-cells, elicit an immune response. Recent developments in T-cell-dependent immunology relating to the immunogenicity of therapeutic products include the descr...

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ژورنال

عنوان ژورنال: Nephrology Dialysis Transplantation

سال: 2003

ISSN: 0931-0509,1460-2385

DOI: 10.1093/ndt/gfg164