AUK12-20

Antibody Name: AUK12-20 (VH SGIIA/JH3 | VL kIII/Jk2)
References: Sato, K., Tsuchiya, M., Saldanha, J., Koishihara, Y., Ohsugi, Y., Kishimoto, T. and Bendig, M. "Humanization of a mouse anti-human interleukin-6 receptor antibody comparing two methods for selecting human framework regions" Mol. Immunol. (1994) 31:371-381.
Donor Antibody: mouse
Acceptor Antibody: Human IgG1 | k
Antigen: human interleukin 6 (IL-6) receptor (different epitope to PM1).
Laboratory: Chugai Pharmaceutical Co, Japan; MRC Collaborative Centre, UK; Osaka University Medical School, Japan
Design: Modelled mouse V regions; use homologous human FRs. Made several versions of the heavy chain.
Frameworks: VH SGI consensus based on mAb 425.
VH HAX (individual human mAb)
VL REI based on Campath-1H.
CDRs: All 6 VH and VL, Kabat Definition.
Backmutations: VH SGI T28S S30T R66K L71V
VH HAX T28S R71V
VL T39K Y71F (plus J region changes of Campath-1H).
Binding: SGI consensus version b bound 90% as well as mouse in competition binding; version a (sle1220Ha) of HAX-based VH bound as well as mouse mAb. Both versions inhibit IL-6-dependent tumour cell growth as well as mouse mAb.
Expression: cos cells with human elongation factor promoter (HEF) vectors
Comment: Highest homology VL FRs were LEN. Individual FRs better than consensus. Consensus sequences may filter out any unusual, and possibly more immunogenic, sequences whereas it may also create an artificial unnatural sequence that could be immunogenic.
Clinical Indication: IL-6 dependent tumours

explanation of symbols and abbreviations

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