title: Exploiting light chains for the scalable generation and platform purification of native human bispecific IgG.
abstract: Bispecific antibodies enable unique therapeutic approaches but it remains a challenge to produce them at the industrial scale, and the modifications introduced to achieve bispecificity often have an impact on stability and risk of immunogenicity. Here we describe a fully human bispecific IgG devoid of any modification, which can be produced at the industrial scale, using a platform process. This format, referred to as a κλ-body, is assembled by co-expressing one heavy chain and two different light chains, one κ and one λ. Using ten different targets, we demonstrate that light chains can play a dominant role in mediating specificity and high affinity. The κλ-bodies support multiple modes of action, and their stability and pharmacokinetic properties are indistinguishable from therapeutic antibodies. Thus, the κλ-body represents a unique, fully human format that exploits light-chain variable domains for antigen binding and light-chain constant domains for robust downstream processing, to realize the potential of bispecific antibodies.
authors: Novimmune SA, 14 chemin des Aulx, CH-1228 Plan-les-Ouates, Switzerland.
authors: Nicolas
authors: N
authors: Fischer
authors: Novimmune SA, 14 chemin des Aulx, CH-1228 Plan-les-Ouates, Switzerland.
authors: Greg
authors: G
authors: Elson
authors: Novimmune SA, 14 chemin des Aulx, CH-1228 Plan-les-Ouates, Switzerland.
authors: Giovanni
authors: G
authors: Magistrelli
authors: Novimmune SA, 14 chemin des Aulx, CH-1228 Plan-les-Ouates, Switzerland.
authors: Elie
authors: E
authors: Dheilly
authors: Novimmune SA, 14 chemin des Aulx, CH-1228 Plan-les-Ouates, Switzerland.
authors: Nicolas
authors: N
authors: Fouque
authors: Novimmune SA, 14 chemin des Aulx, CH-1228 Plan-les-Ouates, Switzerland.
authors: Amélie
authors: A
authors: Laurendon
authors: Novimmune SA, 14 chemin des Aulx, CH-1228 Plan-les-Ouates, Switzerland.
authors: Franck
authors: F
authors: Gueneau
authors: Novimmune SA, 14 chemin des Aulx, CH-1228 Plan-les-Ouates, Switzerland.
authors: Ulla
authors: U
authors: Ravn
authors: Novimmune SA, 14 chemin des Aulx, CH-1228 Plan-les-Ouates, Switzerland.
authors: Jean-François
authors: JF
authors: Depoisier
authors: Novimmune SA, 14 chemin des Aulx, CH-1228 Plan-les-Ouates, Switzerland.
authors: Valery
authors: V
authors: Moine
authors: Novimmune SA, 14 chemin des Aulx, CH-1228 Plan-les-Ouates, Switzerland.
authors: Sylvain
authors: S
authors: Raimondi
authors: Novimmune SA, 14 chemin des Aulx, CH-1228 Plan-les-Ouates, Switzerland.
authors: Pauline
authors: P
authors: Malinge
authors: Novimmune SA, 14 chemin des Aulx, CH-1228 Plan-les-Ouates, Switzerland.
authors: Laura
authors: L
authors: Di Grazia
authors: Novimmune SA, 14 chemin des Aulx, CH-1228 Plan-les-Ouates, Switzerland.
authors: François
authors: F
authors: Rousseau
authors: Novimmune SA, 14 chemin des Aulx, CH-1228 Plan-les-Ouates, Switzerland.
authors: Yves
authors: Y
authors: Poitevin
authors: Novimmune SA, 14 chemin des Aulx, CH-1228 Plan-les-Ouates, Switzerland.
authors: Sébastien
authors: S
authors: Calloud
authors: Novimmune SA, 14 chemin des Aulx, CH-1228 Plan-les-Ouates, Switzerland.
authors: Pierre-Alexis
authors: PA
authors: Cayatte
authors: Novimmune SA, 14 chemin des Aulx, CH-1228 Plan-les-Ouates, Switzerland.
authors: Mathias
authors: M
authors: Alcoz
authors: Novimmune SA, 14 chemin des Aulx, CH-1228 Plan-les-Ouates, Switzerland.
authors: Guillemette
authors: G
authors: Pontini
authors: Novimmune SA, 14 chemin des Aulx, CH-1228 Plan-les-Ouates, Switzerland.
authors: Séverine
authors: S
authors: Fagète
authors: Novimmune SA, 14 chemin des Aulx, CH-1228 Plan-les-Ouates, Switzerland.
authors: Lucile
authors: L
authors: Broyer
authors: Novimmune SA, 14 chemin des Aulx, CH-1228 Plan-les-Ouates, Switzerland.
authors: Marie
authors: M
authors: Corbier
authors: Novimmune SA, 14 chemin des Aulx, CH-1228 Plan-les-Ouates, Switzerland.
authors: Delphine
authors: D
authors: Schrag
authors: Novimmune SA, 14 chemin des Aulx, CH-1228 Plan-les-Ouates, Switzerland.
authors: Gérard
authors: G
authors: Didelot
authors: Novimmune SA, 14 chemin des Aulx, CH-1228 Plan-les-Ouates, Switzerland.
authors: Nicolas
authors: N
authors: Bosson
authors: Novimmune SA, 14 chemin des Aulx, CH-1228 Plan-les-Ouates, Switzerland.
authors: Nessie
authors: N
authors: Costes
authors: Novimmune SA, 14 chemin des Aulx, CH-1228 Plan-les-Ouates, Switzerland.
authors: Laura
authors: L
authors: Cons
authors: Novimmune SA, 14 chemin des Aulx, CH-1228 Plan-les-Ouates, Switzerland.
authors: Vanessa
authors: V
authors: Buatois
authors: Novimmune SA, 14 chemin des Aulx, CH-1228 Plan-les-Ouates, Switzerland.
authors: Zoe
authors: 0000000241202579
authors: Z
authors: Johnson
authors: Novimmune SA, 14 chemin des Aulx, CH-1228 Plan-les-Ouates, Switzerland.
authors: Walter
authors: W
authors: Ferlin
authors: Novimmune SA, 14 chemin des Aulx, CH-1228 Plan-les-Ouates, Switzerland.
authors: Krzysztof
authors: K
authors: Masternak
authors: Novimmune SA, 14 chemin des Aulx, CH-1228 Plan-les-Ouates, Switzerland.
authors: Marie
authors: M
authors: Kosco-Vilbois
mesh_terms: D018033:Antibodies, Bispecific / Q000302:isolation & purification*; D000911:Antibodies, Monoclonal / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D007074:Immunoglobulin G / Q000302:isolation & purification*; D007143:Immunoglobulin Heavy Chains / Q000302:isolation & purification*; D007147:Immunoglobulin Light Chains / Q000378:metabolism; D007145:Immunoglobulin kappa-Chains / Q000378:metabolism; D009500:Neutralization Tests; D019151:Peptide Library; D015202:Protein Engineering / Q000379:methods*; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D018033:Antibodies, Bispecific; D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D007145:Immunoglobulin kappa-Chains; D019151:Peptide Library