BW431/26

Antibody Name: BW431/26 (VH SGIA | VL SGVI)
References: Gussow, D. & Seemann, G. "Humanization of monoclonal antibodies" Meth. Enz. (1991) 203: 99-121.
Donor Antibody: mouse
Acceptor Antibody: Human IgG3 | k
Antigen: Human Carcinoembryonic Antigen (CEA)
Laboratory: MRC, LMB, Cambridge, UK; Behringwerke, Germany
Design: Used consensus sequences from Kabat Ed.IV (1987) to identify unusual amino acids in both the donor (rodent) and acceptor (human) sequences. Put 200% VDW volumes on these positions in the acceptor structures to determine interaction with CDRs. No mention of modelling mouse mAb.
Frameworks: VH NEWM | VL REI (from D1.3).
CDRs: All 6 from VH and VL, Kabat Definition.
Backmutations: S27F:H F29I:H | none in VL (The change at 27 is to the consensus human residue and not the mouse which is a Y)
Binding: Affinity "closely resembles" that of the mouse antibody by competition binding. Binds to purified antigen as well as antigen on tissue sections. 17 out of 18 anti-id mAbs bound to reshaped mAb.
Expression: BHK cells (ATCC CCL10)
Comment: Complete description of design strategy especially comparisons of mouse variable regions with and between consensus sequences. The donor variable regions were highly homologous to the acceptor's by chance.
Clinical Indication: A possible treatment for CEA-producing colorectal, breast and lung carcinomas.

explanation of symbols and abbreviations

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