Human and mouse CD137 have predominantly different binding CRDs to their respective ligands

Monoclonal antibodies (mAbs) to CD137 (a.k.a. 4-1BB) have anti-tumor efficacy in several animal models and have entered clinical trials in patients with advanced cancer. Importantly, anti-CD137 mAbs can also ameliorate autoimmunity in preclinical models. As an approach to better understand the actio...

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Bibliographic Details
Published in:PloS one 2014-01, Vol.9 (1), p.e86337-e86337
Main Authors: Yi, Ling, Zhao, Yanlin, Wang, Xiaojue, Dai, Min, Hellström, Karl Erik, Hellström, Ingegerd, Zhang, Hongtao
Format: Article
Language:English
Subjects:
4-1BB Ligand - metabolism
Analysis
Animal models
Animals
Antibodies, Monoclonal - metabolism
Anticancer properties
Autoimmunity
B cells
Binding
Biology
Cancer
CD137 antigen
Cercopithecus aethiops
Clinical trials
COS Cells
Cysteine - metabolism
Cytokines
Genes
Hospitals
Humans
Kinases
Laboratories
Leukocytes, Mononuclear - metabolism
Ligands
Lymphocytes
Medical research
Medicine
Mice
Monoclonal antibodies
Pathology
Protein Binding - physiology
Recombinant Fusion Proteins - metabolism
T cell receptors
Tuberculosis
Tumor Necrosis Factor Receptor Superfamily, Member 9 - metabolism
Tumor necrosis factor-TNF
Tumors
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Summary:Monoclonal antibodies (mAbs) to CD137 (a.k.a. 4-1BB) have anti-tumor efficacy in several animal models and have entered clinical trials in patients with advanced cancer. Importantly, anti-CD137 mAbs can also ameliorate autoimmunity in preclinical models. As an approach to better understand the action of agonistic and antagonistic anti-CD137 mAbs we have mapped the binding region of the CD137 ligand (CD137L) to human and mouse CD137. By investigating the binding of CD137L to cysteine rich domain II (CRDII )and CRDIII of CD137, we found that the binding interface was limited and differed between the two species in that mouse CD137L mainly combined with CRDII and human CD137L mainly combined with CRDIII.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0086337