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Bispecific Antibody (BsAb) Conjugates

Based on the most advanced techniques and years of experience in antibody engineering field, Creative Biolabs provides custom construction and production services of various bispecific antibodies (BsAbs) and BsAb Conjugates. These diverse services can greatly facilitate your scientific and clinical research about bispecific antibody.

BsAbs have the ability to bind to two different epitopes on the same or on different antigens simultaneously. Different domains of BsAbs can be fused by DNA engineering which is also the prevalent method for producing BsAbs. While a significant number of BsAbs can be derived from chemically crosslinking. By using different starting materials or fusion portions, the BsAb conjugates mainly include the following three classes:

Figure 1. Alternative formats for BsAb conjugates. (Christoph Spiess et al. 2015)

Antibody-antibody conjugates

Ab-Ab bispecific antibody is one format of BsAb conjugates. By the chemical programming approach, the full-length antibody or Fab can be made bispecific and multivalent for each antigen. IgG-IgG, F(ab’)2 and F(ab’)3 are examples of this format. Usually, in the method of chemical conjugation to generate BsAbs, the utilized methodology is often associated with distinct chemistries: intact Igs (IgG-IgG) conjugation relies on amino-reactive reagent while the production of F(ab’)2 and F(ab’)3 utilize sulfhydryl-reactive crosslinkers.

Antibody-peptide conjugates

Besides monoclonal antibodies, various small molecules are also candidate targeting antigens in disease therapy. Antibody-peptide conjugates, also referring to chemically programmed antibodies (cpAbs), are such novel pharmaceuticals utilizing small molecules as the navigator instead of mAb. In these molecules, mAb serves as carrier.

Such two or more pharmacophore peptides can be combinedly used that act as BsAb. In order to have long serum half-life and Ig-like distribution, the antigen-specific peptides can be conjugated with an antibody scaffold, which is also a more recent innovation in the use of conjugation to generate BsAb. The Cov-X-Body is a representative. A bispecific CovX-Body contains two different pharmacophores, both of which covalently bound to deep in the hydrophobic binding pockets on each of the two Fab arms of the scaffold antibody. The pharmacophore peptides of a bispecific Cov-X-Body can be chemically modified and improved for the desired binding affinity, potency, and pharmacokinetics, on the basis of the therapeutic requirement.

BsAb-functionality conjugates

In generation of BsAb, the utilization of crosslinker make it possible to incorporate more functionalities. Some linkers contain an additional reactive group can be used to incorporate other molecules such as cytotoxic drugs, PEG, siRNA, fluorophores, etc. Take the format ScFv1-PEG-scFv2 as an example, this bispecific molecule consists of two scFvs targeting two different antigens and a cross-linker containing PEG. The introduction of PEG into cross-linker can reduce the risks of inactivating the antibody and extend the antibody’s half-life.

Bispecific antibody conjugates are a kind of molecules possessing the advantages of antibody-drug-conjugates and bispecific antibodies. With multi-disciplinary scientists and comprehensive platforms, Creative Biolabs can tailor BsAb development to contribute to your research.

References

1. Spiess, C.; et al. Alternative molecular formats and therapeutic applications for bispecific antibodies. Molecular immunology. 2015, 67(2): 95-106.
2. Doppalapudi, V. R.; et al. Chemical generation of bispecific antibodies. Proc Natl Acad Sci. 2010, 107(52): 22611–22616.

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