BIOMAT Database Logo BIOMAT Database Logo

A strategy for the efficient construction of anti-PD1-based bispecific antibodies with desired IgG-like properties. 2022

Jie Zhao, and Liangfeng Jiang, and Haodong Yang, and Lan Deng, and Xiaoqing Meng, and Jian Ding, and Sixing Yang, and Le Zhao, and Wei Xu, and Xiaolong Wang, and Zhenping Zhu, and Haomin Huang
Research and development, Sunshine Guojian Pharmaceutical (Shanghai) Co. Ltd. A 3SBio Inc. Company, Shanghai, China.

Targeting PD1/PDL1 with blocking antibodies for cancer therapy has shown promising benefits in the clinic, but only approximately 20-30% of patients develop durable clinical responses to the treatment. Bispecific antibodies (BsAbs) that combine PD1/PDL1 blockade with the modulation of another immune checkpoint target may have greater potential to enhance immune checkpoint blockade therapy. In this study, we identified an anti-PD1 monoclonal antibody, 609A, whose heavy chain can pair with a variety of light chains from different antibodies while maintaining its PD1 binding/blocking activity. Taking advantage of this property and using a linear F(ab')2 format, we successfully produced a series of tetravalent IgG-like BsAbs that simultaneously target PD1 and other immune checkpoint targets, including PDL1 and CTLA4. The BsAbs exhibited superior bioactivities in vitro and in vivo compared to their respective parental mAbs. Importantly, the BsAbs demonstrated the desired IgG-like physicochemical properties in terms of high-level expression, ease of purification to homogeneity, good stability and in vivo pharmacokinetics. In summary, we describe a novel and flexible plug-and-play platform to engineer IgG-like BsAbs with excellent development potential for clinical applications.

UI MeSH Term Description Entries
D007074 Immunoglobulin G The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of IgG, for example, IgG1, IgG2A, and IgG2B. Gamma Globulin, 7S,IgG,IgG Antibody,Allerglobuline,IgG(T),IgG1,IgG2,IgG2A,IgG2B,IgG3,IgG4,Immunoglobulin GT,Polyglobin,7S Gamma Globulin,Antibody, IgG,GT, Immunoglobulin
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000911 Antibodies, Monoclonal Antibodies produced by a single clone of cells. Monoclonal Antibodies,Monoclonal Antibody,Antibody, Monoclonal
D016499 Radioimmunotherapy Radiotherapy where cytotoxic radionuclides are linked to antibodies in order to deliver toxins directly to tumor targets. Therapy with targeted radiation rather than antibody-targeted toxins (IMMUNOTOXINS) has the advantage that adjacent tumor cells, which lack the appropriate antigenic determinants, can be destroyed by radiation cross-fire. Radioimmunotherapy is sometimes called targeted radiotherapy, but this latter term can also refer to radionuclides linked to non-immune molecules (see RADIOTHERAPY). Immunoradiotherapy,Immunoradiotherapies,Radioimmunotherapies
D018033 Antibodies, Bispecific Antibodies, often monoclonal, in which the two antigen-binding sites are specific for separate ANTIGENIC DETERMINANTS. They are artificial antibodies produced by chemical crosslinking, fusion of HYBRIDOMA cells, or by molecular genetic techniques. They function as the main mediators of targeted cellular cytotoxicity and have been shown to be efficient in the targeting of drugs, toxins, radiolabeled haptens, and effector cells to diseased tissue, primarily tumors. Bifunctional Antibodies,Bispecific Antibodies,Bispecific Monoclonal Antibodies,Antibodies, Bifunctional,Antibodies, Bispecific Monoclonal,Monoclonal Antibodies, Bispecific
D019138 Antibodies, Blocking Antibodies that inhibit the reaction between ANTIGEN and other antibodies or sensitized T-LYMPHOCYTES (e.g., antibodies of the IMMUNOGLOBULIN G class that compete with IGE antibodies for antigen, thereby blocking an allergic response). Blocking antibodies that bind tumors and prevent destruction of tumor cells by CYTOTOXIC T-LYMPHOCYTES have also been called enhancing antibodies. (Rosen et al., Dictionary of Immunology, 1989) Antibodies, Enhancing,Blocking Antibodies,Enhancing Antibodies

Related Publications

Jie Zhao, and Liangfeng Jiang, and Haodong Yang, and Lan Deng, and Xiaoqing Meng, and Jian Ding, and Sixing Yang, and Le Zhao, and Wei Xu, and Xiaolong Wang, and Zhenping Zhu, and Haomin Huang
Modular Chemical Construction of IgG-like Mono- and Bispecific Synthetic Antibodies (SynAbs).
March 2023, ACS central science,
Jie Zhao, and Liangfeng Jiang, and Haodong Yang, and Lan Deng, and Xiaoqing Meng, and Jian Ding, and Sixing Yang, and Le Zhao, and Wei Xu, and Xiaolong Wang, and Zhenping Zhu, and Haomin Huang
A potential downstream platform approach for WuXiBody-based IgG-like bispecific antibodies.
September 2020, Protein expression and purification,
Jie Zhao, and Liangfeng Jiang, and Haodong Yang, and Lan Deng, and Xiaoqing Meng, and Jian Ding, and Sixing Yang, and Le Zhao, and Wei Xu, and Xiaolong Wang, and Zhenping Zhu, and Haomin Huang
Single variable domain antibody as a versatile building block for the construction of IgG-like bispecific antibodies.
January 2007, Journal of immunological methods,
Jie Zhao, and Liangfeng Jiang, and Haodong Yang, and Lan Deng, and Xiaoqing Meng, and Jian Ding, and Sixing Yang, and Le Zhao, and Wei Xu, and Xiaolong Wang, and Zhenping Zhu, and Haomin Huang
A detergent-based procedure for the preparation of IgG-like bispecific antibodies in high yield.
December 2016, Scientific reports,
Jie Zhao, and Liangfeng Jiang, and Haodong Yang, and Lan Deng, and Xiaoqing Meng, and Jian Ding, and Sixing Yang, and Le Zhao, and Wei Xu, and Xiaolong Wang, and Zhenping Zhu, and Haomin Huang
Recombinant approaches to IgG-like bispecific antibodies.
June 2005, Acta pharmacologica Sinica,
Jie Zhao, and Liangfeng Jiang, and Haodong Yang, and Lan Deng, and Xiaoqing Meng, and Jian Ding, and Sixing Yang, and Le Zhao, and Wei Xu, and Xiaolong Wang, and Zhenping Zhu, and Haomin Huang
Engineering IgG-Like Bispecific Antibodies-An Overview.
August 2018, Antibodies (Basel, Switzerland),
Jie Zhao, and Liangfeng Jiang, and Haodong Yang, and Lan Deng, and Xiaoqing Meng, and Jian Ding, and Sixing Yang, and Le Zhao, and Wei Xu, and Xiaolong Wang, and Zhenping Zhu, and Haomin Huang
Anti-tumor activity of stability-engineered IgG-like bispecific antibodies targeting TRAIL-R2 and LTbetaR.
January 2009, mAbs,
Jie Zhao, and Liangfeng Jiang, and Haodong Yang, and Lan Deng, and Xiaoqing Meng, and Jian Ding, and Sixing Yang, and Le Zhao, and Wei Xu, and Xiaolong Wang, and Zhenping Zhu, and Haomin Huang
IgG-Based Bispecific Anti-CD95 Antibodies for the Treatment of B Cell-Derived Malignancies and Autoimmune Diseases.
August 2022, Cancers,
Jie Zhao, and Liangfeng Jiang, and Haodong Yang, and Lan Deng, and Xiaoqing Meng, and Jian Ding, and Sixing Yang, and Le Zhao, and Wei Xu, and Xiaolong Wang, and Zhenping Zhu, and Haomin Huang
An efficient route to the production of an IgG-like bispecific antibody.
May 2000, Protein engineering,
Jie Zhao, and Liangfeng Jiang, and Haodong Yang, and Lan Deng, and Xiaoqing Meng, and Jian Ding, and Sixing Yang, and Le Zhao, and Wei Xu, and Xiaolong Wang, and Zhenping Zhu, and Haomin Huang
Construction and production of an IgG-Like tetravalent bispecific antibody, IgG-single-chain Fv fusion.
January 2014, Methods in molecular biology (Clifton, N.J.),
Copied contents to your clipboard!