Chimeric and humanized antibodies with specificity for the CD33 antigen

L and H chain cDNAs of M195, a murine mAb that binds to the CD33 Ag on normal and leukemic myeloid cells, were cloned. The cDNAs were used in the construction of mouse/human IgG1 and IgG3 chimeric antibodies. In addition, humanized antibodies were constructed which combined the complementarity-deter...

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Veröffentlicht in:The Journal of immunology (1950) 1992-02, Vol.148 (4), p.1149-1154
Hauptverfasser: Co, MS, Avdalovic, NM, Caron, PC, Avdalovic, MV, Scheinberg, DA, Queen, C
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container_end_page 1154
container_issue 4
container_start_page 1149
container_title The Journal of immunology (1950)
container_volume 148
creator Co, MS
Avdalovic, NM
Caron, PC
Avdalovic, MV
Scheinberg, DA
Queen, C
description L and H chain cDNAs of M195, a murine mAb that binds to the CD33 Ag on normal and leukemic myeloid cells, were cloned. The cDNAs were used in the construction of mouse/human IgG1 and IgG3 chimeric antibodies. In addition, humanized antibodies were constructed which combined the complementarity-determining regions of the M195 antibody with human framework and constant regions. The human framework was chosen to maximize homology with the M195 V domain sequence. Moreover, a computer model of M195 was used to identify several framework amino acids that are likely to interact with the complementarity-determining regions, and these residues were also retained in the humanized antibodies. Unexpectedly, the humanized IgG1 and IgG3 M195 antibodies, which have reshaped V regions, have higher apparent binding affinity for the CD33 Ag than the chimeric or mouse antibodies.
doi_str_mv 10.4049/jimmunol.148.4.1149
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subjects Amino Acid Sequence
Animals
Antibodies, immunoglobulins
Antibodies, Monoclonal - genetics
Antibodies, Monoclonal - immunology
Antibody Affinity
Antigens, CD - immunology
Antigens, Differentiation, Myelomonocytic - immunology
Base Sequence
Biological and medical sciences
Cloning, Molecular
Fundamental and applied biological sciences. Psychology
Fundamental immunology
Humans
Immunoglobulin G - genetics
Immunoglobulin G - immunology
Immunoglobulin Variable Region - genetics
Mice
Molecular immunology
Molecular Sequence Data
Monoclonal antibodies
Recombinant Fusion Proteins - immunology
Sialic Acid Binding Ig-like Lectin 3
title Chimeric and humanized antibodies with specificity for the CD33 antigen
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