BMA 031

Antibody Name: BMA 031 (JH3 | JK5)
References: Shearman, C.W., Pollock, D., White, G., Hehir, K., Moore, G.P., Kanzy, E.J. and Kurrle, R. "Construction, expression and characterization of humanized antibodies directed against the human alpha/beta T cell receptor." J. Immunol. (1991) 147: 4366-4373.
Donor Antibody: mouse
Acceptor Antibody: Human IgG1 | k
Antigen: Human α/B T Cell Receptor (TCR)
Laboratory: Genzyme Corp., MA; Behringwerke Aktiengesellschaft, Germany
Design: Highest homology FRs. First clear account of using consensus sequences in the design (Kabat Ed IV 1987). However, lacked model-building to "prioritize" importance of residues which were different from the consensus of the mouse and human subgroups. When there was no clear consensus residue, they kept the human FR. Kept residues within 4 positions of every CDR as mouse (or similar). Made two versions of both heavy and light chains.
Frameworks: VH EU | VL EU using the most homologous J regions (JH4 | JK4)
CDRs: All 6 VH and VL, Kabat Definition.
Backmutations: VH G27Y T28K S30T R38K M48I R66K V67A I69L F89V Y90H F91Y G94R
VL I21M L46R L47W M48I S60A
Binding: Best version (CIV-3) had 2.5-fold reduction in affinity compared to the mouse mAb as measured by competitive immunofluorescence assays. Potent at mediating killing (ADCC) of HPB-ALL cells.
Expression: mouse Sp2/0 myeloma cells
Comment: Use of consensus sequences from both mouse and human. Special mention of residues 69:H 89-91:H 94:H and 48:L as being highly unusual and within four residues of a CDR. Suggestion of using germline (or consensus) FRs to limit number of backmutations.
Clinical Indication: May be used in transplantation, graft versus host, autoimmunity and other T cell-related problems.

explanation of symbols and abbreviations

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