SK2

Antibody Name: SK2 (VH SGI | VL kV)
References: Sato, K., Ohtomo, T., Hirata, Y., Saito, H., Matsuura, T., Akimoto, T., Akamatsu, K-i., Koishihara, Y., Ohsugi, Y. and Tsuchiya, M. "Humanization of an anti-human IL-6 mouse monoclonal antibody glycosylated in its heavy chain variable region" Hum. Antibod. Hybridoma (1996) 7:175-183.
Donor Antibody: mouse
Acceptor Antibody: Human IgG1 | k
Antigen: human IL-6 (epitopes: receptor binding site (I) and gp130 interaction domain (II), this mAb probably recognises an epitope close to both sites).
Laboratory: Chugai Pharmaceutical Co. Ltd., Japan
Design: Highest homology to VH SG II (DAW) and kI (REI). Modelled V regions plus carbohydrate moiety on glycosylation site.
Frameworks: VH DAW | VL REI (as in Campath-1H).
CDRs: All 6 VH and VL, Kabat Definition.
Backmutations: F71Y:L
Binding: Affinity constants (Kd)(Kon/Koff) were measured by surface plasmon resonance on BIAcore (Pharmacia) machine. The two versions of the light chain showed good Ag-binding activity. However, the F71Y change gave better results in functional (binding inhibition) assays.
Expression: Transient expression in cos-7 cells and stable CHO transformants.
Comment: N-glycosylation site at position 30:H (Canonical for CDR-H1, N instead of usual S). Experiments with deglycosylated mAbs showed it did not significantly influence Ag/Ab interaction (contrast with M195).
Clinical Indication: Increased levels of IL-6 in sepsis, AIDS, rheumatoid arthritis and cardiac myxoma. IL-6 is a growth factor for malignant cells in plasmacytoma/myeloma and mesangial glomerulonephritis. It is an autocrine/paracrine factor in osteoclasts in Paget's disease.

explanation of symbols and abbreviations

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