Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.5.1.1 (asparaginase)
 2,695 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An extra-corporeal chamber has been constructed and used for diagnosis, enzyme therapy and immuno-adsorption. The chamber is made from polymethyl-acrylate and the dimensions of the chamber are 10 x 18 x 7 cm. It contains 23 plates with a total area of 0.5 m2. In most cases no pump is used. The active substance is bound covalently to the plate surfaces. The time for each hemoperfusion has been 3-6 hr. No infections, decrease of thrombocytes or other side effects have been observed. By immobilized homologous antisera (F (ab')2), three putative tumour-associated antigens were isolated from cases of hypernephroma. Two children and one adult patient with malignant lymphoma were treated with extra-corporeal L-asparaginase, the latter with repeated remissions of metastases. The level of antibodies against Factor VIII was significantly decreased by chamber immunoadsorption in two cases of hemophilia. A number of kidney transplantation cases received extra-corporeal L-asparaginase pre- and post-operatively to counteract rejection. In all around 50 patients have received extra-corporeal treatment without any adverse effects. The use of the extra-corporeal chamber in other diseases is discussed.
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PMID:Enzyme therapy and immuno-adsorption by an extra-corporeal device. 698 19

All biotherapeutics have the potential to induce an immune response. This immunological response is complex and, in addition to antibody formation, involves T cell activation and innate immune responses that could contribute to adverse effects. Integrated immunogenicity data analysis is crucial to understanding the possible clinical consequences of anti-drug antibody (ADA) responses. Because patient- and product-related factors can influence the immunogenicity of a therapeutic protein, a risk-based approach is recommended and followed by most drug developers to provide insight over the potential harm of unwanted ADA responses. This paper examines mitigation strategies currently implemented and novel under investigation approaches used by drug developers. The review describes immunomodulatory regimens used in the clinic to mitigate deleterious ADA responses to replacement therapies for deficiency syndromes, such as hemophilia A and B, and high risk classical infantile Pompe patients (e.g., cyclophosphamide, methotrexate, rituximab); novel in silico and in vitro prediction tools used to select candidates based on their immunogenicity potential (e.g., anti-CD52 antibody primary sequence and IFN beta-1a formulation); in vitro generation of tolerogenic antigen-presenting cells (APCs) to reduce ADA responses to factor VIII and IX in murine models of hemophilia; and selection of novel delivery systems to reduce in vivo ADA responses to highly immunogenic biotherapeutics (e.g., asparaginase). We conclude that mitigation strategies should be considered early in development for biotherapeutics based on our knowledge of existing clinical data for biotherapeutics and the immune response involved in the generation of these ADAs.
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PMID:Approaches to Mitigate the Unwanted Immunogenicity of Therapeutic Proteins during Drug Development. 2808 96