Pipeline and MOA (mechanism of action) of bispecific antibodies (BsAbs)

Bridge of 2 cells (engagers)

By binding with 2 antigens from 2 different cells, the BsAbs can physically link them together, thus these kinds of BsAbs are named “engagers”. The redirecting of immune cells to tumor cells by the engagers makes the immune cell activated and then eliminate the target cells. The T cell engagers are the most popular BsAbs which account for nearly half of the clinical trials aimed evaluating the BsAbs. NK cell engagers are recently developed BsAbs for NK cell-dependent tumor cell elimination.

The engagers in research, clinical trials and market are listed below. Genemedi offers the high quality, premade benchmark BsAbs for researchers.

Targeting multiple receptors

Bridging receptors is an obligate mechanism in which the binding of BsAbs to 2 receptors causes the activation or inhibition of each receptor. The co-activation or inhibition synergistically enhanced the biological effect of single antibody.

ligand redundancy

In addition to bind to the receptors, targeting redundancy for cytokines or angiogenesis factors represents an area of interest for BsAbs.

Biparatopic bsAbs

Instead of targeting two different proteins, bsAbs may be designed to simultaneously bind to two non-overlapping epitopes on the same target. Biparatopic targeting builds on increasing binding strength through antigen crosslinking and aggregation, thereby mimicking effects observed for antibody mixtures and polyclonal antibodies. Biparatopic bsAbs are therefore essentially a combinatorial concept

Cofactor mimetics

BsAbs can also be designed as a scaffold or cofactor linking enzyme and substrate together. One of the applications is the BsAbs used as a substitution of a critical clotting factor in the treatment of hemophilia.

Piggyback approaches

Exploit the first binding specificity of a BsAb as a transport modality for the second specificity are named the “piggyback” approaches. To cross the blood-brain barrier, one binding arm of the BsAbs are designed to target the transferrin receptor (TfR). The human serum albumin (HSA) targeting domain are used to extent the half-life of BsAbs, especially to BsAbs without Fc, for example the tandem ScFvs or VHHs. In addition, the piggyback approaches are also been used in promoting the degradation of pathogens.

Introduction about bispecific antibodies (BsAbs)

Bispecific antibodies (BsAbs) are designed to bind two different epitopes or antigens, which leads to multiple mechanistic functions with synergistic effects. The attractive feature is their potential for novel functionalities, which do not exist in mixtures of the parental or reference antibodies. Till now, more than 200 BsAb-based clinical trails have been registered on and 4 BsAbs (with one withdraw) have been granted FDA approval. The promising future makes BsAbs attracting more attentions.

The connecting of two specificities within one BsAb can be exploited for novel therapeutic concepts. The mostly applications of BsAbs are recruiting effector cells to the target cells, which are regarded as the immune cell engagers. The redirection of the cytotoxic effector cells (T and NK cells) to the targeting cancer cells by BsAbs physically link them together and activate the effector cells to eliminate the target ones. In addition, the BsAbs can also be used to link two molecules together to make the therapeutic effects such as the dual inhibition of immune checkpoints, the conditionally activate a growth factor receptor for diabetes treatment and the replacement of natural bridge molecules such as the coagulation factor VIII. More innovative designs of BsAbs can be achieved in the future.

To accelerate the development of BsAbs, Genemedi offers the high quality, premade benchmark BsAbs for researchers. The biosimilars are expressed by mammalian cell line and used for biological drug discovery items including cell culture, assay development, animal model development, PK/PD model development (Pharmacokinetics & Pharmacodynamic) and mechanism of action (MOA) research.

Formats of bispecific antibodies (BsAbs)

Many formats have been developed for BsAb generation as listed in the following table.

Bispecific Antibody Development Programs Guidance for Industry by FDA

FDA set up the guidance for the development of BsAbs. The link and PDF files are listed below.

Bispecific Antibody Development Programs Guidance for Industry

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