How to Generate Three Common Types of Bispecific Antibody Conjugates?

May 12 18:44 2021 Vivian Creative Print This Article

Bispecific Antibodies (bsAbs), a type of artificial proteins that can simultaneously bind to two different and unique antigens (or different epitopes of the same antigen), are widely used for both academic and clinical purposes. It's admitted that genetic engineering is the most prevalent method to generate bsAbs, while a variety of cross-linked antibodies (known as bispecific antibody conjugates) can also be generated by different chemical strategies.

An antibody conjugate consists of a monoclonal antibody (or fragment thereof),Guest Posting a chemical linker, and a biologically active cytotoxic payload or drug. The selection of conjugated molecules depends on the research purpose and the conjugation method.

Distinguished by different starting materials, crosslinkers, fusion portions, etc., three main classes of the bsAb conjugates are developed for scientific and clinical research.

  • Antibody-Antibody Conjugates
  • Antibody-Peptide Conjugates
  • Antibody-Functionality Conjugates 

Antibody-Antibody Conjugates

Antibody-antibody conjugates are generated by conjugating two different whole antibodies together to get a 300kDa bispecific molecule that has the bivalent binding capability for each antigen. 

Creative Biolabs, one of the most recognized antibody service providers, can apply different starting antibodies, crosslinking reagents, and conjugation strategies to generate different qualified antibody-antibody conjugates, such as IgG-IgG bsAbs, F(ab')2, and F(ab')3 bsAbs to satisfy the specific research needs.

The synthesis of IgG-IgG bsAbs is based on the amino-reactive reagents that target lysine side-chains. Meanwhile, the crosslinkers used to conjugate IgG-IgG are usually hetero-bifunctional. In contrast to the generation of IgG-IgG bsAbs, F(ab')2 and F(ab')3 bsAbs are usually formed depending on homo-bifunctional reagents.

Antibody-Peptide Conjugates 

Besides antibodies, the functional portions of bispecific molecules targeting antigens also include some small drugs or peptides. Antibody-peptide conjugates are chemically programmed novel pharmaceuticals that use small molecules as the navigator rather than the traditional mAbs.

These small molecules grant bsAb conjugates not only high affinity but also easy access to various cells, making antibody-peptides conjugates excellent therapeutic agents to manufacture.

Antibody-Functionality Conjugates

Chemical conjugation also allows using crosslinkers that have reactive groups to conjugate the target antibody. For instance, ScFv1-PEG-scFv2 bsAb from Creative Biolabs has three reactive groups, including two scFvs targeting two different antigens and a cross-linker containing PEG. Additional reactive groups, including fluorophores, simulating peptides, PEG, siRNA, and cytotoxic drugs are likely to enhance in vivo pharmacokinetics/pharmacodynamics (PK/PD) profile or the targeted mechanism of action. 

Different from antibody-peptide conjugates, antibody-functionality conjugate retains the reactivity of antibody moieties and the property of additional functionalities rather than simply using antibody portions as carriers.


Generating bispecific antibody conjugates mainly depends on what materials and methods are used, and the strategies of DNA engineering and chemically crosslinking take a significant part in bsAb conjugate generation.

As researchers hold an optimistic attitude toward bsAbs in the application of autoimmune diseases, inflammatory diseases, cancer, etc., large-scale generation and purity should be the core task for biotechnology companies. Creative Biolabs, as a leading expert for bispecific antibody development and production, takes advantage of advanced techniques and comprehensive platforms and is making efforts to streamline and qualify bsAb conjugate construction and production. Find more information at

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Vivian Creative
Vivian Creative

Enthusiastic science communicators and freelancer with a simple mission - to make science exciting and present it in an innovative, interesting, and engaging style, and discover science full of curiosity and eager to learn more.

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