Cloning, expression and characterization of monkey (Macaca fascicularis) CD137
Shen-Jue Chen1, William R Foster, Maria N Jure-Kunkel
1Discovery Toxicology, Bristol-Myers Squibb Research and Development, Route 206 & Province Line Road, Princeton, NJ 08543, United States. shenjue.chen@bms.com
Veterinary Immunology and Immunopathology
|September 6, 2008
Summary
Researchers characterized cynomolgus monkey CD137, finding sequence variants and polymorphisms distinct from human CD137. This highlights potential differences in antibody pharmacologic activity between species and individuals.
Area of Science:
- Immunology
- Molecular Biology
- Pharmacology
Background:
- CD137 is a co-stimulatory molecule crucial for T cell activation.
- Agonistic CD137 antibodies are explored as cancer immunotherapies by activating T cells.
Purpose of the Study:
- To clone and characterize cynomolgus monkey CD137 for pre-clinical evaluation.
- To compare monkey CD137 with human CD137, focusing on sequence, variants, and antibody binding.
Main Methods:
- Cloning and sequencing of cynomolgus monkey CD137.
- Identification of splice variants and single nucleotide polymorphisms (SNPs).
- mRNA expression analysis in peripheral blood mononuclear cells (PBMCs) and antibody binding assays.
Main Results:
- Monkey CD137 shares 95% amino acid identity with human CD137 but has distinct extracellular domain sequences.
- Four splice variants and two missense SNPs were identified in monkey CD137.
- Both full-length and variant CD137 mRNA expression increased in PBMCs upon anti-CD3 stimulation.
- An anti-human CD137 antibody bound recombinant monkey CD137, but an anti-mouse antibody did not.
Conclusions:
- Cynomolgus monkey CD137 exhibits unique sequence polymorphisms and variants compared to human CD137.
- Antibody efficacy may differ between species and among individual monkeys due to these variations.
- Characterization is essential for accurate pre-clinical assessment of CD137-targeted therapies.
