Immune response to enzyme replacement therapy: single epitope control of antigen distribution from circulation.
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 alpha-L-iduronidase immunized rats, representing a model of the lysosomal storage disorder Hurler syndrome (alpha-L-iduronidase deficiency). The antibody response to alpha-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 alpha-L-iduronidase was used to reproduce the in vivo effect of altered enzyme tissue distribution, previously observed in immunized rats infused with alpha-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.
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal; D004195:Disease Models, Animal; D018604:Epitope Mapping; D000939:Epitopes / Q000235:genetics; D006801:Humans; D007068:Iduronidase / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000627:therapeutic use*; D007114:Immunization; D008247:Lysosomes / Q000201:enzymology; D051379:Mice; D008969:Molecular Sequence Data; D008059:Mucopolysaccharidosis I / Q000188:drug therapy / Q000201:enzymology / Q000276:immunology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
D000911:Antibodies, Monoclonal; D000939:Epitopes; D007068:Iduronidase