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Advances in antibody engineering have led to the generation of more innovative antibody drugs, such as bispecific antibodies (bsAbs). Following the success associated with blinatumomab, bsAbs have attracted enormous interest in the field of cancer immunotherapy. By specifically targeting two different antigens, bsAbs reduce the distance between tumor and immune cells, thereby enhancing tumor killing directly. There are several mechanisms of action upon which bsAbs have been exploited. Accumulating experience on checkpoint-based therapy has promoted the clinical transformation of bsAbs targeting immunomodulatory checkpoints. Cadonilimab (PD-1 × CTLA-4) is the first approved bsAb targeting dual inhibitory checkpoints, which confirms the feasibility of bsAbs in immunotherapy. In this review we analyzed the mechanisms by which bsAbs targeting immunomodulatory checkpoints and their emerging applications in cancer immunotherapy.


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Bispecific antibodies targeting immunomodulatory checkpoints for cancer therapy

Show Author's information Tiancheng Zhang1,*Youpei Lin1,*Qiang Gao1,2,3( )
Department of Liver Surgery and Transplantation, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China
Key Laboratory of Medical Epigenetics and Metabolism, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China
State Key Laboratory of Genetic Engineering, Fudan University, Shanghai 200433, China

*These authors contributed equally to this work.

Abstract

Advances in antibody engineering have led to the generation of more innovative antibody drugs, such as bispecific antibodies (bsAbs). Following the success associated with blinatumomab, bsAbs have attracted enormous interest in the field of cancer immunotherapy. By specifically targeting two different antigens, bsAbs reduce the distance between tumor and immune cells, thereby enhancing tumor killing directly. There are several mechanisms of action upon which bsAbs have been exploited. Accumulating experience on checkpoint-based therapy has promoted the clinical transformation of bsAbs targeting immunomodulatory checkpoints. Cadonilimab (PD-1 × CTLA-4) is the first approved bsAb targeting dual inhibitory checkpoints, which confirms the feasibility of bsAbs in immunotherapy. In this review we analyzed the mechanisms by which bsAbs targeting immunomodulatory checkpoints and their emerging applications in cancer immunotherapy.

Keywords: immunotherapy, tumor microenvironment, clinical trials, Antibody–drug conjugate, bispecific antibody

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Publication history
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Publication history

Received: 02 January 2023
Accepted: 14 February 2023
Published: 24 March 2023
Issue date: March 2023

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©2023 Cancer Biology & Medicine.

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