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Optimizing assembly and production of native bispecific antibodies by codon de-optimization.

ABSTRACT: When production of bispecific antibodies requires the co-expression and assembly of three or four polypeptide chains, low expression of one chain can significantly limit assembly and yield. ?? bodies, fully human bispecific antibodies with native IgG structure, are composed of a common heavy chain and two different light chains, one kappa and one lambda. No engineering is applied to force pairing of the chains, thus both monospecific and bispecific antibodies are secreted in the supernatant. In this context, stoichiometric expression of the two light chains allows for maximal assembly of the bispecific antibody. In this study, we selected a ?? body with suboptimal characteristics due to low kappa chain expression. Codon optimization to increase expression of the kappa chain did not improve bispecific yield. Surprisingly, progressive introduction of non-optimal codons into the sequence of the lambda chain resulted in lowering its expression for an optimal tuning of the relative distribution of monospecific and bispecific antibodies. This codon de-optimization led to doubling of the ?? body yield. These results indicate that assembly of different proteins into a recombinant complex is an interconnected process and that reducing the expression of one polypeptide can actually increase the overall yield.

SUBMITTER: Magistrelli G

PROVIDER: S-EPMC5297534 | biostudies-literature | 2017 Feb/Mar

REPOSITORIES: biostudies-literature

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Optimizing assembly and production of native bispecific antibodies by codon de-optimization.

Magistrelli Giovanni G Poitevin Yves Y Schlosser Florence F Pontini Guillemette G Malinge Pauline P Josserand Soheila S Corbier Marie M Fischer Nicolas N

mAbs 20170201 2

When production of bispecific antibodies requires the co-expression and assembly of three or four polypeptide chains, low expression of one chain can significantly limit assembly and yield. κλ bodies, fully human bispecific antibodies with native IgG structure, are composed of a common heavy chain and two different light chains, one kappa and one lambda. No engineering is applied to force pairing of the chains, thus both monospecific and bispecific antibodies are secreted in the supernatant. In ...[more]

PMID: 28001485

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Dataset Information

Optimizing assembly and production of native bispecific antibodies by codon de-optimization.

Publications

Optimizing assembly and production of native bispecific antibodies by codon de-optimization.

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