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Bispecific Antibodies - Current Status and Prospects
EP38621
Poster Title: Bispecific Antibodies - Current Status and Prospects
Submitted on 12 Apr 2022
Author(s): Sunny Fang
Affiliations: Biochempeg Scientific Inc.
Poster Views: 496
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Poster Information
Abstract: Bispecific antibodies (BsAbs) are antibodies with two binding sites, directed against two different antigens or two different epitopes on the same antigen. BsAbs are clinically superior to monoclonal antibodies (MoAbs) and have a wide range of applications in tumor immunotherapy as well as in the treatment of other diseases such as hemophilia A, diabetes, Alzheimer's disease and ophthalmological diseases. Currently, four BsAbs have received market approval, more than 180 BsAbs are in preclinical development, and over 50 BsAbs have been investigated in clinical trials.

Bispecific Antibodies

How Do Bispecific Antibodies Work?
Since BsAbs have two binding sites for different antigens or recognize two different epitopes of an antigen simultaneously, their functional pathways are quite flexible. There are four main mechanisms of action of bispecific antibodies.

▶ Recruiting and activating of immune cells to to exert their killing effect
▶ Blocking of dual signaling pathways
▶ Blocking of immune checkpoints
▶ Forcing association of protein complexes

Recruiting And Activating Of Immune Cells

An important mechanism of action of bispecific antibodies is to activate immune cells. Bispecific antibodies have two antigen-binding arms, one of which binds to the target antigen and the other to a labeled antigen on the effector cell (T cells and NK cells are commonly used), which activates the effector cell and allows it to target and kill tumor cells. CD3 is currently a popular immune cell surface target for bispecific antibodies development, with a greater ability to activate and recruit T cells.

The design of this bispecific antibody focuses on selecting a reasonable range of antibody affinities to inhibit Fc-mediated effector functions as much as possible while having stronger specificity for tumor targets. The marketed blinatumomab (targeting CD3×CD19) removes the Fc structure and reduces the risk of T cell overactivation. Both antibodies use single-chain antibody fragments that do not have an intact IgG structure, reducing CD3 affinity. The CD19 target with high tumor specificity was also selected, with relatively good safety.
Summary: Bispecific antibodies (BsAbs) are antibodies with two binding sites, directed against two different antigens or two different epitopes on the same antigen. BsAbs are clinically superior to monoclonal antibodies (MoAbs) and have a wide range of applications in tumor immunotherapy as well as in the treatment of other diseases such as hemophilia A, diabetes, Alzheimer's disease and ophthalmological diseases. Currently, four BsAbs have received market approval, more than 180 BsAbs are in preclinicalReferences: [1] Esfandiari et al., (2022). Bispecific antibodies in oncology. Nature Reviews Drug Discovery, https://doi.org/10.1038/d41573-022-00040-2
[2] Ma J, Mo Y, Tang M, Shen J, Qi Y, Zhao W, Huang Y, Xu Y, Qian C. Bispecific Antibodies: From Research to Clinical Application. Front Immunol. 2021 May 5;12:626616. doi: 10.3389/fimmu.2021.626616. PMID: 34025638; PMCID: PMC8131538.
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