Open AccessReshaping a therapeutic CD4 antibody.
Author(s) -
Scott D. Gorman,
Mike Clark,
E. G. Routledge,
Stephen Cobbold,
Herman Waldmann
Publication year - 1991
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.88.10.4181
Subject(s) - antibody , avidity , autoimmunity , biology , mutagenesis , in vitro , immunology , chimera (genetics) , virology , computational biology , microbiology and biotechnology , genetics , gene , mutation
An immunosuppressive rat antibody (Campath-9) against human CD4 has been reshaped for use in the management of autoimmunity and the prevention of graft rejection. Two different forms of the reshaped antibody were produced that derive their heavy chain variable region framework sequences from the human myeloma proteins KOL or NEW. When compared to a chimeric form of the CD4 antibody, the avidity of the KOL-based reshaped antibody was only slightly reduced, whereas that of the NEW-based reshaped antibody was very poor. The successful reshaping to the KOL-based framework was by a procedure involving the grafting of human framework sequences onto the cloned rodent variable region by in vitro mutagenesis.