Reshaping a therapeutic CD4 antibody.
Open Access
- 15 May 1991
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 88 (10) , 4181-4185
- https://doi.org/10.1073/pnas.88.10.4181
Abstract
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.Keywords
This publication has 31 references indexed in Scilit:
- The induction of skin graft tolerance in major histocompatibility complex‐mismatched or primed recipients: primed T cells can be tolerized in the periphery with anti‐CD4 and anti‐CD8 antibodiesEuropean Journal of Immunology, 1990
- Induction of tolerance in peripheral T cells with monoclonal antibodiesEuropean Journal of Immunology, 1990
- Framework residue 71 is a major determinant of the position and conformation of the second hypervariable region in the VH domains of immunoglobulinsJournal of Molecular Biology, 1990
- Induction of classical transplantation tolerance in the adult.The Journal of Experimental Medicine, 1989
- Acquisition of an additional antigen specificity after mouse CD4 gene transfer into a T helper hybridoma.The Journal of Experimental Medicine, 1988
- Immunological unresponsiveness induced by recipient cells transfected with donor MHC genesNature, 1988
- Replacing the complementarity-determining regions in a human antibody with those from a mouseNature, 1986
- Induction of tolerance by monoclonal antibody therapyNature, 1986
- Amino acid sequence of the VH region of a human myeloma immunoglobulin (IgG New)Biochemistry, 1977
- Molecular structure of a dimer composed of the variable portions of the Bence-Jones protein REI refined at 2.0-Å resolutionBiochemistry, 1975