Urelumab
From Wikipedia, the free encyclopedia
| Monoclonal antibody | |
|---|---|
| Type | Whole antibody |
| Source | Human |
| Target | CD137 |
| Clinical data | |
| Other names | BMS-663513 |
| ATC code |
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| Identifiers | |
| CAS Number | |
| ChemSpider |
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| UNII | |
| KEGG | |
| Chemical and physical data | |
| Formula | C6502H9972N1712O2030S44 |
| Molar mass | 146015.89 g·mol−1 |
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Urelumab (BMS-663513 or anti-4-1BB antibody) is a fully human, non‐ligand binding, CD137 agonist immunoglobulin‐γ 4 (IgG4) monoclonal antibody.[1] It was developed utilizing Medarex's UltiMAb(R) technology by Bristol-Myers Squibb for the treatment of cancer and solid tumors.[2] Urelumab promotes anti-tumor immunity, or an immune response against tumor cells, via CD137 activation.[2][3] The application of Urelumab has been limited because it can cause severe liver toxicity.[4][5][6]
Urelumab targets the extracellular domain of CD137 (4-1BB).[7]
CD137 is a co-stimulatory molecule that’s a member of the tumor necrosis factor (TNF) receptor superfamily.[4] The CD137 gene is located within the chromosome 1 p36 locus.[8] CD137 is expressed on the surfaces of activated CD8+ and CD4+ T cells, natural killer (NK) cells, dendritic cells, B cells, monocytes, and neutrophils.[4] Urelumab targets, binds to, and activates the CD137 receptor on these CD137-expressing immune cells.[2]
The activation of CD137 signaling by urelumab promotes anti-tumor immunity through a variety of mechanisms.[2][3]
CD137 activation by urelumab stimulates a strong cytotoxic T cell response against tumor cells which results in tumor clearance.[8] Urelumab achieves this by promoting the proliferation and survival of activated CD8+ T cells and upregulating their activity and effector functioning by allowing for increased levels of cytokine production (IL-2 and IFN‐γ) and higher cytotoxic capacity of activated CD8+ T cells.[2][5][8] It also results in increased formation of memory T cells, which is crucial for creating a long-term anti-tumor response.[8]
CD137 activation by urelumab also strengthens other aspects of the innate and adaptive immune response against tumor cells. CD137 activation promotes the proliferation and survival of natural killer cells which carry out antibody-dependent cell-mediated cytotoxicity of tumor cells.[2] CD137 activation also promotes the proliferation and survival of B cells and CD4+ T cells, the differentiation of monocytes into dendritic cells, and the secretion of cytokines from these cell types.[8]