Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Animals
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Antibodies, Monoclonal / genetics*
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Antibodies, Monoclonal / immunology
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Antibody Affinity
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Antigens, CD / immunology*
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Antigens, Differentiation, Myelomonocytic / immunology*
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Base Sequence
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Cloning, Molecular
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Humans
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Immunoglobulin G / genetics*
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Immunoglobulin G / immunology
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Immunoglobulin Variable Region / genetics
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Mice
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Molecular Sequence Data
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Recombinant Fusion Proteins / immunology*
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Sialic Acid Binding Ig-like Lectin 3
Substances
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Antibodies, Monoclonal
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Antigens, CD
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Antigens, Differentiation, Myelomonocytic
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CD33 protein, human
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Cd33 protein, mouse
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Immunoglobulin G
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Immunoglobulin Variable Region
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Recombinant Fusion Proteins
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Sialic Acid Binding Ig-like Lectin 3
Associated data
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GENBANK/L19643
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GENBANK/L19644
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GENBANK/L19645
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GENBANK/L19646
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GENBANK/L19647
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GENBANK/M65172
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GENBANK/M65173
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GENBANK/M65174
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GENBANK/M83098
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GENBANK/M83099