Exploiting light chains for the scalable generation and platform purification of native human bispecific IgG
نویسندگان
چکیده
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.
منابع مشابه
BEAT® the bispecific challenge: a novel and efficient platform for the expression of bispecific IgGs
Background The binding of two biological targets with a single IgGbased molecule is thought to be beneficial for clinical efficacy. However the technological challenges for the development of a bispecific platform are numerous. While correct pairing of heterologous heavy and light chains (Hc and Lc) can be achieved by engineering native IgG scaffolds, crucial properties such as thermostability,...
متن کاملA new approach for generating bispecific antibodies based on a common light chain format and the stable architecture of human immunoglobulin G1.
Bispecific antibodies combine two different antigen-binding sites in a single molecule, enabling more specific targeting, novel mechanisms of action, and higher clinical efficacies. Although they have the potential to outperform conventional monoclonal antibodies, many bispecific antibodies have issues regarding production, stability, and pharmacokinetic properties. Here, we describe a new appr...
متن کاملDevelopment and characterization of polyclonal antibody against human kappa light chain in rabbit
Polyclonal antibodies against kappa light chain are used to diagnose diseases producing free light chain. The kappa and lambda light chains are products of immunoglobulin synthesis and released into the circulation in minor amounts such as serum, cerebrospinal fluid, urine and synovial fluid in normal condition. The purpose of this study was the production and purification of polyclonal immunog...
متن کاملDevelopment of purification processes for fully human bispecific antibodies based upon modification of protein A binding avidity
There is strong interest in the design of bispecific monoclonal antibodies (bsAbs) that can simultaneously bind 2 distinct targets or epitopes to achieve novel mechanisms of action and efficacy. Multiple bispecific formats have been proposed and are currently under development. Regeneron's bispecific technology is based upon a standard fully human IgG antibody in order to minimize immunogenicit...
متن کاملCompatibility of B-Sheets with Epitopes Predicted by Immunoinformatic in Human IgG
Background & Aims: Antibodies, well-known as immunoglobulins (Igs), are produced by B lymphocytes and specifically defend against pathogens. Igs are glycoproteins and have high diagnostic value in several diseases including infections (1). Igs are composed of light and heavy chains (2, 3). Each chain is comprised of about 110-120 amino acid residues which create immunoglobulin folds named domai...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
دوره 6 شماره
صفحات -
تاریخ انتشار 2015