A cytokine-neutralizing antibody as a structural mimetic of 2 receptor interactions.
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ABSTRACT:
SUBMITTER: Grutter C
PROVIDER: S-EPMC2600578 | biostudies-literature | 2008 Dec
REPOSITORIES: biostudies-literature
Publications
A cytokine-neutralizing antibody as a structural mimetic of 2 receptor interactions.
Grütter Christian C Wilkinson Trevor T Turner Richard R Podichetty Sadhana S Finch Donna D McCourt Matthew M Loning Scott S Jermutus Lutz L Grütter Markus G MG
Proceedings of the National Academy of Sciences of the United States of America 20081210 51
TGF-beta isoforms are key modulators of a broad range of biological pathways and increasingly are exploited as therapeutic targets. Here, we describe the crystal structures of a pan-TGF-beta neutralizing antibody, GC-1008, alone and in complex with TGF-beta3. The antibody is currently in clinical evaluation for idiopathic pulmonary fibrosis, melanoma, and renal cell cancer. GC-1008 recognizes an asymmetric binding interface across the TGF-beta homodimer with high affinity. Whereas both cognate r ...[more]
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