Curtin University Homepage
  • Library
  • Help
    • Admin

    espace - Curtin’s institutional repository

    JavaScript is disabled for your browser. Some features of this site may not work without it.
    View Item 
    • espace Home
    • espace
    • Curtin Research Publications
    • View Item
    • espace Home
    • espace
    • Curtin Research Publications
    • View Item

    Characterization of a unique conformational epitope on free immunoglobulin kappa light chains that is recognized by an antibody with therapeutic potential

    Access Status
    Fulltext not available
    Authors
    Hutchinson, A.
    Alexova, R.
    Bockhorni, V.
    Ramsland, Paul
    Jones, D.
    Jennings, C.
    Broady, K.
    Edmundson, A.
    Raison, R.
    Date
    2011
    Type
    Journal Article
    
    Metadata
    Show full item record
    Citation
    Hutchinson, A. and Alexova, R. and Bockhorni, V. and Ramsland, P. and Jones, D. and Jennings, C. and Broady, K. et al. 2011. Characterization of a unique conformational epitope on free immunoglobulin kappa light chains that is recognized by an antibody with therapeutic potential. Molecular Immunology. 48 (9-10): pp. 1245-1252.
    Source Title
    Molecular Immunology
    DOI
    10.1016/j.molimm.2011.03.003
    ISSN
    0161-5890
    School
    School of Biomedical Sciences
    URI
    http://hdl.handle.net/20.500.11937/23510
    Collection
    • Curtin Research Publications
    Abstract

    The murine mAb, K-1-21, recognizes a conformational epitope expressed on free Ig kappa light chains (FκLCs) and also on cell membrane-associated FκLCs found on kappa myeloma cells. This has led to the development of a chimeric version of K-1-21, MDX-1097, which is being assessed in a Phase II clinical trial for the treatment of multiple myeloma. The epitope recognized by K-1-21 is of particular interest, especially in the context that it is not expressed on heavy chain-associated light chains such as in an intact Ig molecule. Using epitope excision techniques we have localized the K-1-21 epitope to a region spanning residues 104–110 of FκLC. This short strand of residues links the variable and constant domains, and is a flexible region that adopts different conformations in FκLC and heavy chain-associated light chain. We tested this region using site-directed mutations and found that the reactivity of K-1-21 for FκLC was markedly reduced. Finally, we applied in silico molecular docking to generate a model that satisfied the experimental data. Given the clinical potential of the Ag, this study may aid the development of next generation compounds that target the membrane form of FκLC expressed on the surface of myeloma plasma cells.

    Related items

    Showing items related by title, author, creator and subject.

    • Structural glycobiology of antibody recognition in xenotransplantation and cancer immunotherapy
      Agostino, Mark; Farrugia, W.; Sandrin, M.; Scott, A.; Yuriev, E.; Ramsland, Paul (2012)
      Carbohydrate antigens recognized by “natural” or preformed and elicited antibodies are central to transplantation/transfusion rejection across ABO blood group and species (xenotransplantation) barriers and are also promising ...
    • Construction of single-chain Fv with two possible CDR3H conformations but similar inter-molecular forces that neutralize bovine herpesvirus 1
      Koti, M.; Farrugia, W.; Nagy, E.; Ramsland, Paul; Kaushik, A. (2010)
      Bovine herpesvirus 1 (BoHV-1) causes respiratory and genital diseases in cattle for which available vaccines do not confer adequate protection. Since passive immunization with antibodies permits disease prevention, ...
    • A commentary on agility in humanitarian aid supply chains
      Oloruntoba, Richard ; Kovács, G. (2015)
      © 2015, Emerald Group Publishing Limited. Purpose – This paper aims to provide a commentary and an overview of developments in the field of humanitarianism that could impact theoretical understanding of agility in ...
    Advanced search

    Browse

    Communities & CollectionsIssue DateAuthorTitleSubjectDocument TypeThis CollectionIssue DateAuthorTitleSubjectDocument Type

    My Account

    Admin

    Statistics

    Most Popular ItemsStatistics by CountryMost Popular Authors

    Follow Curtin

    • 
    • 
    • 
    • 
    • 

    CRICOS Provider Code: 00301JABN: 99 143 842 569TEQSA: PRV12158

    Copyright | Disclaimer | Privacy statement | Accessibility

    Curtin would like to pay respect to the Aboriginal and Torres Strait Islander members of our community by acknowledging the traditional owners of the land on which the Perth campus is located, the Whadjuk people of the Nyungar Nation; and on our Kalgoorlie campus, the Wongutha people of the North-Eastern Goldfields.