A bispecific antibody (BsAb) is an artificial antibody that can simultaneously bind two separate, specific antigens or different epitopes of the same antigen and establish a bridge between target cells and functional molecules to stimulate a directed immune response. This genetically engineered antibody has become a research hotspot in the field of antibody engineering and has an extensive prospect in immunotherapy for various diseases.

Fig.1 Mechanism of Catumaxomab BsAb.¹ There are mainly two formats of bispecific antibodies (BsAbs), including the immunoglobulin G (IgG)-based molecule and non-IgG-based (single-chain-based) molecule. The primary application of BsAbs is to redirect cytotoxic immune effector cells to enhance the killing effect on by antibody-dependent cell-mediated cytotoxicity (ADCC) as well as other cytotoxic substances mediated by effector cells.

Fig.1 Mechanism of blinatumomab therapeutic action. (Sedykh, 2018)

BsAbs do not exist in nature and thus they are produced by molecular, genetic, or biochemical approaches. With the evolving of technology of recombinant protein derivatives, many BsAbs have become therapeutic proteins. In Creative Biolabs, our proprietary BsAb technology constitute a suite of highly flexible platforms with multiple valuable options, eliminating the drug development challenge and offering attractive therapeutics for tumors.

Bespecific Antibody (BsAb) Platforms at Creative Biolabs

Fig.2 Some classic structures of BsAbs with CD3 as one of their targets.¹

BsAb is the next generation of antibody therapeutics, which combines two or more antigen-recognizing elements into a single framework, and can bind to two or more target cells. It accounts for a theory that more than one pathway is usually at the root of disease. Creative Biolabs has advanced recombinant antibody technology and many other technology platforms to effectively immortalize the best hybridoma clones, which helps extend our antibody production and engineering capability.

■ BsAb Construction Platforms

The key point of BsAbs is that they bind two antigens simultaneously, leading to a wide range of concepts for the construction of various version of this antibody. As a result, a large number of tools for manufacturing BsAb are gradually emerging. Nowadays, the application of BsAbs has been expanded from conventional cancer immunotherapy to other diseases, such as AIDS, infections, and genetic diseases.

• Quadroma technology – It allows to produce antibodies in a single host cell but results in a mixture of tailored and other unfunctional compounds.
• CrossMab technology – It is based on the exchanging light chain and heavy chain domains within a unique Fab arm to induce special interaction while maintaining the orgininal antigen binding affinity.
• Linkers technology – Conjunction two parts of antibody fragment via specific linkers with different lengths.
• Molecular cloning technology – Multiple DNA components are assembled to direct their replication within host cells.
• Knobs-into-holes (KIH) technology – It is employed to force heavy chain of antibody heterodimerization over homodimerization.
• Asymmetric re-engineering technology (ART) – A novel technique is invented by Japan scientists for asymmetric BsAbs.

■ Other Unique BsAb Platforms

The practice of research and diversity of antibody forms have explained that a unique BsAb format cannot meet all requirements. There are several examples of formats in preclinical or clinical trials indicating the strong potential of this type of compounds as biotherapeutics.

• DART – Bispecific antibody fragment, a diabody comprising the variable domains of two distinct antibodies;
• sdAb – Bispecific antibody fragment, its bispecificity obtained by connecting two sdAbs by short linkers;
• κλ-BODY – Bispecific IgG, a fully human bispecific IgG antibody;
• SEEDbody – Bispecific IgG-like, strand-exchange engineered domain is an alternation of human IgG and IgA sequence in the CH3 domain.

Creative Biolabs possesses seasoned experts and long-term experience in the development of all kinds of therapeutic antibodies. With the help of us, clients can select the optimal BsAb products and obtain the very detailed of the scientific knowledge linked to the antibody field.

■ Features & Advantages

✔ Time-saving and inexpensive: Saving at least 6 months and reducing the cost by half;
✔ Powerful platforms: allowing for almost any mAb sequence to build bispecifics;
✔ High expression level: Optimized HEK293 or CHO (5-15 g/L) mammalian cell systems;
✔ Multiple purification ways (> 95%): Protein A/G affinity purification, chromatography;
✔ Optional formats: Available in both symmetric and asymmetric molecules;
✔ High qualities: very stable, soluble (> 30 mg/ml), low immunogenicity;
✔ Potent QC analysis: MS, SEC-HPLC, activity assay, endotoxin test, etc.

■ Characteristic Services at Creative Biolabs

Over the past decades, great advances in bioengineering and expanded insight in onco-immunology have resulted in the emergence of novel BsAb constructs. Clinical studies have currently shown impressive results of BsAb in terms of immune effector cell retargeting, target-dependent activation and the induction of anti-tumor responses.

In Creative Biolabs, we have designed and manufactured a variety of BsAbs through our powerful, open-access techniques, and the further development can be expected to successfully take BsAb approaches forward. Our services included but not limited to:

BsAb is considered to be applicable to biomedical needs and has increasingly been of interest in diagnostic and therapeutic areas. If there is any question, please contact us for more information.

Reference

1. Ma, Jiabing, et al. "Bispecific antibodies: from research to clinical application." Frontiers in Immunology 12 (2021): 626616.

For Research Use Only | Not For Clinical Use

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