κλ-body Generation Service

Creative Biolabs is an indubitable leader of the antibodies development and manufacture. With professional scientists and years of rich experience, we offer a variety of high quality bispecific antibody (BsAb) development service, such as κλ-body generation, to meet every client’s requirements.

Ideally, a BsAb should be undistinguishable from a standard human IgG molecule. Although clear clinical potential and therapeutic benefits have gained in the past years, there are still some great challenges to develop and generate BsAbs at the industrial scale in sufficient quantity and purity. The extensive application of BsAbs has also been impeded by the difficulty of identifying BsAbs formats which show favorable pharmacokinetic properties. Besides, modifications introduced to give bispecificity usually have an impact on stability and risk of immunogenicity.

κλ-body

κλ-body is generated by a unique technology platform, which facilitates to create unmodified fully human BsAbs, utilizing a generic downstream purification process with industrial-scale manufacturing. This approach is achieved by the production of in vitro display libraries with common heavy chains which are used to select against two different antigens. In this way, candidates with different target specificities can be separated, science they use the same heavy chain but carry either κ or λ light chains. Three different chains (one heavy and two light) are then co-expressed in a single cell to form a mixture comprising two mAb species (one κ and one λ) and a BsAb comprising a κ and a λ light chain. Therefore, BsAbs formed in this manner enable to be efficiently purified from the mAb species and other contaminants through highly selective affinity resins binding to either human κ or λ constant domains. According to its structure, this fully human BsAb format is named as a κλ-body.

Figure. Schematic diagram of the production of bispecific IgG based on light-chain diversity. Part A shows the parallel discovery of two bispecific arms from a fixed VH library and part B shows the sequential discovery of a second arm compatible with an existing antibody. (Fischer, N., 2015)

Advantages of κλ-body

The κλ-bodies hold multiple modes of action, and their stability and pharmacokinetic properties are undistinguishable from therapeutic antibodies. Hence, compared to existing engineered formats, κλ-bodies are unique in providing the classical functional and biochemical properties of a human antibody. Following are some remarkable advantages of κλ-bodies:

• It can readily be expressed at high level via a standard CHO expression system.
• It has all the favorable properties required, for example, stability, platform manufacturability, extended half-life, effector function and low intrinsic immunogenicity.
• It represents the ideal BsAb format, due to its indistinguishable from a standard fully human monoclonal antibody.
• Scale-up at a 100L pilot scale has been successfully performed.

With our well-established κλ-body technology platform, the experienced scientists here at Creative Biolabs are dedicated to helping you develop unique BsAbs. We also provide other various services regarding BsAbs development. Please feel free to contact us for more information and a detailed quote.

References

1. Fischer, N.; et al. “Exploiting light chains for the scalable generation and platform purification of native human bispecific IgG.” Nature communications. 2015, 6: 6113.
2. Spiess, C.; et al. “Alternative molecular formats and therapeutic applications for bispecific antibodies.” Molecular immunology. 2015, 67(2): 95-106.