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.
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
View the Knowledge base of Bispecific antibodies:
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