7D4B

Crystal structure of 4-1BB in complex with a VHH

Summary for 7D4B

• Entry DOI: 10.2210/pdb7d4b/pdb
• Descriptor: Tumor necrosis factor receptor superfamily member 9, anti-4-1BB VHH, alpha-D-mannopyranose-(1-3)-alpha-D-mannopyranose-(1-6)-[alpha-D-mannopyranose-(1-3)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose, ... (8 entities in total)
• Functional Keywords: antibody, complex, vhh, immune system
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 31206.71

Authors

Wang, C. (deposition date: 2020-09-23, release date: 2021-07-14, Last modification date: 2024-10-16)

Primary citation

Zhai, T.,Wang, C.,Xu, Y.,Huang, W.,Yuan, Z.,Wang, T.,Dai, S.,Peng, S.,Pang, T.,Jiang, W.,Huang, Y.,Zou, Y.,Xu, Y.,Sun, J.,Gong, X.,Zhang, J.,Tsun, A.,Li, B.,Miao, X.
Generation of a safe and efficacious llama single-domain antibody fragment (vHH) targeting the membrane-proximal region of 4-1BB for engineering therapeutic bispecific antibodies for cancer.
J Immunother Cancer, 9:-, 2021

PubMed Abstract: The discovery of checkpoint inhibitors towards cytotoxic T-lymphocyte protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1) has been revolutionary for the treatment of cancers. These therapies have only offered an average of 20%-30% response rates across the tumor spectrum and the combination of agonists towards the tumor-necrosis superfamily members, such as 4-1BB and CD40, has shown potent efficacy in preclinical studies; however, these agonists have exhibited high degrees of toxicity with limited efficacy in human trials. In this study, we have generated a single-domain antibody towards a unique epitope of 4-1BB that limits its potential on-target toxicity while maintaining sufficient potency. This 4-1BB binder is ideal for use in the engineering of multispecific antibodies to localize 4-1BB activation within the tumor microenvironment, as shown here by a anti-PD-L1/4-1BB bispecific candidate (PM1003).

PubMed: 34172514
DOI: 10.1136/jitc-2020-002131

Experimental method

X-RAY DIFFRACTION (3.14 Å)