7VUX

Complex structure of PD1 and 609A-Fab

Summary for 7VUX

• Entry DOI: 10.2210/pdb7vux/pdb
• Descriptor: Programmed cell death protein 1, Heavy chain of Fab fragment, Light chain of Fab fragment, ... (10 entities in total)
• Functional Keywords: pd1 fab complex, immune system
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 3
• Total formula weight: 63178.27

Authors

Huang, H.,Zhu, Z.,Zhao, J.,Jiang, L.,Yang, H.,Deng, L.,Meng, X.,Ding, J.,Yang, S.,Zhao, L.,Xu, W.,Wang, X. (deposition date: 2021-11-04, release date: 2021-11-17, Last modification date: 2024-10-16)

Primary citation

Zhao, J.,Jiang, L.,Yang, H.,Deng, L.,Meng, X.,Ding, J.,Yang, S.,Zhao, L.,Xu, W.,Wang, X.,Zhu, Z.,Huang, H.
A strategy for the efficient construction of anti-PD1-based bispecific antibodies with desired IgG-like properties.
Mabs, 14:2044435-2044435, 2022

PubMed Abstract: 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') 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.

PubMed: 35239451
DOI: 10.1080/19420862.2022.2044435

Experimental method

X-RAY DIFFRACTION (1.64 Å)