PM-1

Antibody Name: PM-1 (VH SGII | kI)
References: Sato, K., Tsuchiya, M., Saldanha, J., Koishihara, Y., Ohsugi, Y., Kishimoto, T. and Bendig, M.M. "Reshaping a human antibody to inhibit the interleukin 6-dependent tumor cell growth" Canc. Res. (1994) 53:851-856.
Tsunenari, T., Akamatsu, K., Kaiho, S., Sato, K., Tsuchiya, M., Koishihara, Y., Kishimoto, T. and Ohsugi, Y. "Therapeutic potential of humanized anti-interleukin-6 receptor antibody: Antitumor activity in xenograft model of multiple myeloma" Anticancer Res. (1996) 16:2537.
Donor Antibody: mouse
Acceptor Antibody: Human IgG1 | k
Antigen: human interleukin 6 receptor
Laboratory: Chugai Pharmaceutical Co. & Osaka University Medical School, Japan; MRC Collaborative Centre, UK
Design: Homology search revealed VH VAP (SGII) and VL REI (SGI). A model was built of the mouse variable regions. Six versions of the heavy chain and 2 of the light chain.
Frameworks: VH NEWM | VL REI (from D1.3)
CDRs: All 6 VH and VL, Kabat Definition.
Backmutations: VH STFS27-30YSIT V71R
VL none (except those of Riechmann et al, (1988)).
Binding: Best binder, version VH(f)| VL(a) by competition binding assays. Binds "as well as" chimaeric and mouse mAbs. Inhibits growth of multiple myeloma cells.
Expression: Transient expression in cos cells with human elongation factor (HEF) vectors; stable expression in CHO DHFR- cells
Comment: In heavy chain, position 1 and 48 also tested but no influence on binding.
F71:L kept human, Y in mouse caused worse binding!
Clinical Indication: Multiple myeloma patients. The disease is always lethal and few therapeutic treatments are available.

explanation of symbols and abbreviations

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