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PDBsum entry 4gos
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Immune system
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PDB id
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4gos
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References listed in PDB file
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Key reference
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Title
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Structure and cancer immunotherapy of the b7 family member b7X.
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Authors
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H.Jeon,
V.Vigdorovich,
S.C.Garrett-Thomson,
M.Janakiram,
U.A.Ramagopal,
Y.M.Abadi,
J.S.Lee,
L.Scandiuzzi,
K.C.Ohaegbulam,
J.M.Chinai,
R.Zhao,
Y.Yao,
Y.Mao,
J.A.Sparano,
S.C.Almo,
X.Zang.
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Ref.
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Cell Rep, 2014,
9,
1089-1098.
[DOI no: ]
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PubMed id
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Abstract
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B7x (B7-H4 or B7S1) is a member of the B7 family that can inhibit T cell
function. B7x protein is absent in most normal human tissues and immune cells,
but it is overexpressed in human cancers and often correlates with negative
clinical outcome. The expression pattern and function of B7x suggest that it may
be a potent immunosuppressive pathway in human cancers. Here, we determined the
crystal structure of the human B7x immunoglobulin variable (IgV) domain at 1.59
Å resolution and mapped the epitopes recognized by monoclonal antibodies. We
developed an in vivo system to screen therapeutic monoclonal antibodies against
B7x and found that the clone 1H3 significantly inhibited growth of
B7x-expressing tumors in vivo via multiple mechanisms. Furthermore, the
surviving mice given 1H3 treatment were resistant to tumor rechallenge. Our data
suggest that targeting B7x on tumors is a promising cancer immunotherapy and
humanized 1H3 may be efficacious for immunotherapy of human cancers.
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