5GGV

CTLA-4 in complex with tremelimumab Fab

Summary for 5GGV

• Entry DOI: 10.2210/pdb5ggv/pdb
• Related: 5GGQ 5GGR 5GGS 5GGT 5GGU
• Descriptor: light chain, heavy chain, Cytotoxic T-lymphocyte protein 4, ... (4 entities in total)
• Functional Keywords: antibody, immune system
• Biological source: Homo sapiens (Human); More
• Cellular location: Cell membrane ; Single-pass type I membrane protein : P16410
• Total number of polymer chains: 3
• Total formula weight: 62868.27

Authors

Heo, Y.S. (deposition date: 2016-06-16, release date: 2016-11-09, Last modification date: 2016-11-16)

Primary citation

Lee, J.Y.,Lee, H.T.,Shin, W.,Chae, J.,Choi, J.,Kim, S.H.,Lim, H.,Won Heo, T.,Park, K.Y.,Lee, Y.J.,Ryu, S.E.,Son, J.Y.,Lee, J.U.,Heo, Y.S.
Structural basis of checkpoint blockade by monoclonal antibodies in cancer immunotherapy
Nat Commun, 7:13354-13354, 2016

PubMed Abstract: Cancer cells express tumour-specific antigens derived via genetic and epigenetic alterations, which may be targeted by T-cell-mediated immune responses. However, cancer cells can avoid immune surveillance by suppressing immunity through activation of specific inhibitory signalling pathways, referred to as immune checkpoints. In recent years, the blockade of checkpoint molecules such as PD-1, PD-L1 and CTLA-4, with monoclonal antibodies has enabled the development of breakthrough therapies in oncology, and four therapeutic antibodies targeting these checkpoint molecules have been approved by the FDA for the treatment of several types of cancer. Here, we report the crystal structures of checkpoint molecules in complex with the Fab fragments of therapeutic antibodies, including PD-1/pembrolizumab, PD-1/nivolumab, PD-L1/BMS-936559 and CTLA-4/tremelimumab. These complex structures elucidate the precise epitopes of the antibodies and the molecular mechanisms underlying checkpoint blockade, providing useful information for the improvement of monoclonal antibodies capable of attenuating checkpoint signalling for the treatment of cancer.

PubMed: 27796306
DOI: 10.1038/ncomms13354

Experimental method

X-RAY DIFFRACTION (1.998 Å)