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PDBsum entry 5ggt
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Immune system
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PDB id
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5ggt
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Contents |
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116 a.a.
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216 a.a.
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210 a.a.
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References listed in PDB file
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Key reference
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Title
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Structural basis of checkpoint blockade by monoclonal antibodies in cancer immunotherapy.
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Authors
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J.Y.Lee,
H.T.Lee,
W.Shin,
J.Chae,
J.Choi,
S.H.Kim,
H.Lim,
T.Won heo,
K.Y.Park,
Y.J.Lee,
S.E.Ryu,
J.Y.Son,
J.U.Lee,
Y.S.Heo.
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Ref.
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Nat Commun, 2016,
7,
13354.
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PubMed id
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Abstract
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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.
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