C21

Antibody Name: C21 (TES-C21)
References: Kolbinger, F., Saldanha, J., Hardman, N. and Bendig, M. "Humanization of a mouse anti-human IgE antibody: a potential therapeutic for IgE-mediated allergies" Prot. Engng. (1993) 6:971-980.
Donor Antibody: mouse
Acceptor Antibody: Human IgG1 | k
Antigen: human IgE free and bound to B-cells, but not to FcRI or FcRII (CD23) on mast cells and basophils
Laboratory: Ciba-Geigy AG, Switzerland; MRC Collaborative Centre, UK (original mouse mAb from Tannox Biosystems, TX)
Design: Model mouse V regions. Tried using homologous FRs from consensus sequences and individual human mAbs. Made several versions.
Frameworks: Consensus VH SGI | VL kIII from Kabat Ed IV, 1987
Individual mAbs VH HAY | VL KAF
CDRs: All 6 VH and VL, Kabat Definition.
Backmutations: VH Q43H V67A M69F L71A S94R
VL E1D V3L Y49K D60S
Binding: Little difference between consensus or individual human FRs. Best versions bind slightly better than mouse or chimaeric mAbs as measured by Pharmacia BIAcore (biosensor-based analytical) system. Version L1/H3 being developed in the clinic.
Expression: transient expression in cos cells, later stable expression in NS0
Comment: Genentech also has anti-IgE humanised mAb MaE11.
Clinical Indication: Immediate-type hypersensitivities such as extrinsic bronchial asthma, hayfever, allergic rhinitis and food/drug allergies.

explanation of symbols and abbreviations

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