Chimeric and humanized antibodies with specificity for the CD33 antigen

Man Sung Co, Nevenka M. Avdalovic, Philip C. Caron, Mark V Avdalovic, David A. Scheinberg, Cary Queen

Research output: Contribution to journalArticle

120 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1149-1154
Number of pages6
JournalJournal of Immunology
Volume148
Issue number4
StatePublished - Feb 15 1992
Externally publishedYes

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Sialic Acid Binding Ig-like Lectin 3
Antibodies, Monoclonal, Humanized
Antibody Specificity
Immunoglobulin G
Complementarity Determining Regions
Complementary DNA
Antibodies
Myeloid Cells
Computer Simulation
Amino Acids

ASJC Scopus subject areas

  • Immunology

Cite this

Co, M. S., Avdalovic, N. M., Caron, P. C., Avdalovic, M. V., Scheinberg, D. A., & Queen, C. (1992). Chimeric and humanized antibodies with specificity for the CD33 antigen. Journal of Immunology, 148(4), 1149-1154.

Chimeric and humanized antibodies with specificity for the CD33 antigen. / Co, Man Sung; Avdalovic, Nevenka M.; Caron, Philip C.; Avdalovic, Mark V; Scheinberg, David A.; Queen, Cary.

In: Journal of Immunology, Vol. 148, No. 4, 15.02.1992, p. 1149-1154.

Research output: Contribution to journalArticle

Co, MS, Avdalovic, NM, Caron, PC, Avdalovic, MV, Scheinberg, DA & Queen, C 1992, 'Chimeric and humanized antibodies with specificity for the CD33 antigen', Journal of Immunology, vol. 148, no. 4, pp. 1149-1154.
Co MS, Avdalovic NM, Caron PC, Avdalovic MV, Scheinberg DA, Queen C. Chimeric and humanized antibodies with specificity for the CD33 antigen. Journal of Immunology. 1992 Feb 15;148(4):1149-1154.
Co, Man Sung ; Avdalovic, Nevenka M. ; Caron, Philip C. ; Avdalovic, Mark V ; Scheinberg, David A. ; Queen, Cary. / Chimeric and humanized antibodies with specificity for the CD33 antigen. In: Journal of Immunology. 1992 ; Vol. 148, No. 4. pp. 1149-1154.
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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.",
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