BrE-3

Antibody Name: BrE-3 (SGIIIC|kII)
References: Couto, J.R., Blank, E.W., Peterson, J.A., Kiwan, R., Padlan, E.A. and Ceriani, R.L. "Engineering of antibodies for breast cancer Therapy: Construction of chimaeric and humanized versions of the murine monoclonal antibody BrE-3" In "Antigen and Antibody Molecular Engineering in Breast Cancer Diagnosis and Treatment" (1994) Ed. Ceriani, R.L., Plenum Press, New York pp55-59.
Donor Antibody: mouse
Acceptor Antibody: Human IgG1 | k
Antigen: Tandem repeat of the polypeptide core of human breast mucin.
Laboratory: Cancer Research Fund of Contra Costa, CA; NIH, MD
Design: Priorities: Preserve binding affinity and diminish immunogenicity. Basically positional consensus approach (veneering). Many of retained residues occur in human sequences of the same subgroup. Constructed three progressively more human versions.
Frameworks: SGIII|kII consensus sequences.
CDRs: All 6 VH and VL, Kabat Definition.
Backmutations: Not stated but 9 mouse residues left in VH and 6 in VL FRs.
Binding: Increased affinity in competition binding assays. Ruled out N-glycosylation, since the pattern was not there, but raised the possibility of O-glycosylation causing the increase.
Expression: Mouse myeloma cell line Sp2/0-Ag14
Comment: Chimaeric mAb established authenticity of isolated cDNAs and provided fallback option if the humanised had failed.
Clinical Indication: Human breast cancer.

explanation of symbols and abbreviations

José Saldanha © 1997-8. Birkbeck College, London WC1E 7HX.