Immune response to enzyme replacement therapy: Single epitope control of antigen distribution from circulation

Elias N. Glaros; Chris T. Turner; Emma J. Parkinson; John J. Hopwood; Doug A. Brooks

doi:10.1016/S1096-7192(02)00148-8

Immune response to enzyme replacement therapy: Single epitope control of antigen distribution from circulation

Elias N. Glaros, Chris T. Turner, Emma J. Parkinson, John J. Hopwood, Doug A. Brooks

Hopwood Centre For Neurobiology

Research output: Contribution to journal › Article › peer-review

8 Citations (Scopus)

Abstract

Immune response to replacement therapy has been reported for a range of therapeutic strategies being developed for the treatment of patients with genetic disease. The potential problem of immune response to enzyme replacement therapy has been investigated in α-L-iduronidase immunized rats, representing a model of the lysosomal storage disorder Hurler syndrome (α-Liduronidase deficiency). The antibody response to α-L-iduronidase showed that the positional location of antibody reactivity was similar for different immunized rats, but the precise linear sequence epitopes identified, varied between rats. A monoclonal antibody reacting to an epitope in close proximity to one high antigenicity site on α-L-iduronidase was used to reproduce the in vivo effect of altered enzyme tissue distribution, previously observed in immunized rats infused with α-L-iduronidase. The study demonstrated that during an immune response, antibody reacting to a single epitope could partially control the tissue distribution of antigen from circulation.

Original language	English
Pages (from-to)	127-135
Number of pages	9
Journal	Molecular Genetics and Metabolism
Volume	77
Issue number	1-2
DOIs	https://doi.org/10.1016/S1096-7192(02)00148-8
Publication status	Published or Issued - 2002

Keywords

Antibodies
Epitopes
Genetic disease
Immune response
Therapy

ASJC Scopus subject areas

Endocrinology, Diabetes and Metabolism
Biochemistry
Molecular Biology
Genetics
Endocrinology

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10.1016/S1096-7192(02)00148-8

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title = "Immune response to enzyme replacement therapy: Single epitope control of antigen distribution from circulation",

abstract = "Immune response to replacement therapy has been reported for a range of therapeutic strategies being developed for the treatment of patients with genetic disease. The potential problem of immune response to enzyme replacement therapy has been investigated in α-L-iduronidase immunized rats, representing a model of the lysosomal storage disorder Hurler syndrome (α-Liduronidase deficiency). The antibody response to α-L-iduronidase showed that the positional location of antibody reactivity was similar for different immunized rats, but the precise linear sequence epitopes identified, varied between rats. A monoclonal antibody reacting to an epitope in close proximity to one high antigenicity site on α-L-iduronidase was used to reproduce the in vivo effect of altered enzyme tissue distribution, previously observed in immunized rats infused with α-L-iduronidase. The study demonstrated that during an immune response, antibody reacting to a single epitope could partially control the tissue distribution of antigen from circulation.",

keywords = "Antibodies, Epitopes, Genetic disease, Immune response, Therapy",

author = "Glaros, {Elias N.} and Turner, {Chris T.} and Parkinson, {Emma J.} and Hopwood, {John J.} and Brooks, {Doug A.}",

note = "Funding Information: This work was supported by a NH & MRC Program Grant in Australia, the Rebecca L. Cooper Medical Research Foundation and the Women{\textquoteright}s and Children{\textquoteright}s Hospital Research Foundation, Adelaide, Australia. The authors gratefully acknowledge the technical assistance of Leanne Hein for α- l -iduronidase immunopurification and enzyme assay, Ayan Dasvarma for epitope mapping the monoclonal antibodies, Dyane Auclair and Allison Crawley for handling of the rats, and Christine Boulter for cell culture.",

year = "2002",

doi = "10.1016/S1096-7192(02)00148-8",

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pages = "127--135",

journal = "Molecular Genetics and Metabolism",

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T2 - Single epitope control of antigen distribution from circulation

AU - Glaros, Elias N.

AU - Turner, Chris T.

AU - Parkinson, Emma J.

AU - Hopwood, John J.

AU - Brooks, Doug A.

N1 - Funding Information: This work was supported by a NH & MRC Program Grant in Australia, the Rebecca L. Cooper Medical Research Foundation and the Women’s and Children’s Hospital Research Foundation, Adelaide, Australia. The authors gratefully acknowledge the technical assistance of Leanne Hein for α- l -iduronidase immunopurification and enzyme assay, Ayan Dasvarma for epitope mapping the monoclonal antibodies, Dyane Auclair and Allison Crawley for handling of the rats, and Christine Boulter for cell culture.

PY - 2002

Y1 - 2002

N2 - Immune response to replacement therapy has been reported for a range of therapeutic strategies being developed for the treatment of patients with genetic disease. The potential problem of immune response to enzyme replacement therapy has been investigated in α-L-iduronidase immunized rats, representing a model of the lysosomal storage disorder Hurler syndrome (α-Liduronidase deficiency). The antibody response to α-L-iduronidase showed that the positional location of antibody reactivity was similar for different immunized rats, but the precise linear sequence epitopes identified, varied between rats. A monoclonal antibody reacting to an epitope in close proximity to one high antigenicity site on α-L-iduronidase was used to reproduce the in vivo effect of altered enzyme tissue distribution, previously observed in immunized rats infused with α-L-iduronidase. The study demonstrated that during an immune response, antibody reacting to a single epitope could partially control the tissue distribution of antigen from circulation.

AB - Immune response to replacement therapy has been reported for a range of therapeutic strategies being developed for the treatment of patients with genetic disease. The potential problem of immune response to enzyme replacement therapy has been investigated in α-L-iduronidase immunized rats, representing a model of the lysosomal storage disorder Hurler syndrome (α-Liduronidase deficiency). The antibody response to α-L-iduronidase showed that the positional location of antibody reactivity was similar for different immunized rats, but the precise linear sequence epitopes identified, varied between rats. A monoclonal antibody reacting to an epitope in close proximity to one high antigenicity site on α-L-iduronidase was used to reproduce the in vivo effect of altered enzyme tissue distribution, previously observed in immunized rats infused with α-L-iduronidase. The study demonstrated that during an immune response, antibody reacting to a single epitope could partially control the tissue distribution of antigen from circulation.

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KW - Epitopes

KW - Genetic disease

KW - Immune response

KW - Therapy

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Immune response to enzyme replacement therapy: Single epitope control of antigen distribution from circulation

Abstract

Keywords

ASJC Scopus subject areas

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