Duration: 3 min
Jeffery Shi
Protein and Antibody Product Marketing
Jeffrey Shi, Head of Protein and Antibody Product Marketing Team of Marketing
Department. He and his team are responsible for customer-centric development of full product
life cycle management for Protein and Antibody, and drive the sustainable development of the
protein antibody business.
Bispecific antibodies (bsAbs) are emerging as promising biotherapeutics for a growing
range of diseases. In recent years, bsAbs have seen rapid development in fields such as tumor immunotherapy,
anti-infection treatments, and autoimmune diseases. Compared to monoclonal antibodies, bsAbs offer several
therapeutic advantages due to their additional specific antigen-binding sites:
Enhanced efficacy
One of the key mechanisms of bsAbs is their ability to mediate immune cell killing.
BsAbs possess two antigen-binding arms: one binds to the target antigen, while the other binds to a
marker antigen on the effector cell. This dual binding can activate the effector cell to target and
destroy tumor cells. Two bsAbs products currently approved for marketing demonstrate this mechanism.
Catumaxomab, developed by Trion Pharma, targets the tumor surface antigen EpCAM and the T cell
surface receptor CD3 [1]. Similarly, Blinatumomab, developed by Amgen, binds to both CD19
and CD3.
Both drugs achieve tumor treatment by activating and recruiting killer T cells [2].
Preventing drug resistance
BsAbs can block dual signaling pathways by binding to two targets simultaneously. Receptor
tyrosine kinases (RTKs) are a major class of enzyme-linked receptors that play a crucial role in cell
proliferation, such as the Her family. RTKs are often overexpressed on the surface of tumor cells, leading
to malignant cell proliferation, making them important targets for tumor treatment. While monoclonal
antibodies targeting single RTK targets have been widely used, tumor cells can escape immune detection by
altering signaling pathways or activating intracellular signals through homologous or heterologous dimers
between HER family members or different members. BsAbs can simultaneously block two or more RTKs or their
ligands, thereby reducing tumor cell escape and improving treatment efficacy [3].
Reduce toxicity
The two antigen-binding arms of bsAbs can target different antigens. By binding to two antigens
on the surface of cancer cells, bsAbs enhance the binding specificity and targeting of antibodies to cancer
cells, thereby reducing off-target effects and associated side effects.
Reduce treatment costs
Compared to traditional antibodies, bsAbs offer strong competitiveness in terms of tissue
penetration rate, tumor cell killing efficiency, off-target rate, and clinical indications. They have
significant clinical advantages, particularly in dosage. Since their therapeutic effect can be 100 to 1000
times that of ordinary antibodies, the dosage can be reduced to as low as 1/2000 of the original amount,
significantly lowering the cost of drug treatment. Additionally, compared to combination therapy, the cost
of bsAbs is much lower than that of using two single agents.
In summary, bispecific antibodies hold
substantial promise in enhancing therapeutic efficacy,
preventing drug resistance, reducing toxicity, and lowering treatment costs, making them a valuable addition
to modern biotherapeutics.
References
[1] https://en.wikipedia.org/wiki/Catumaxomab
[2]
https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-blinatumomab-consolidation-cd19-positive-philadelphia-chromosome-negative-b-cell
[3] Fan G, Wang Z, Hao M, Li J. Bispecific antibodies and their applications. J Hematol Oncol.
2015 Dec 21;8:130. doi: 10.1186/s13045-015-0227-0.
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