Urelumab is a fully humanized agonistic monoclonal antibody targeting the CD137 receptor with potential immunostimulatory and antineoplastic activities. Urelumab specifically binds to and activates CD137-expressing immune cells, stimulating an immune response, in particular a cytotoxic T cell response, against tumor cells. Urelumab has been used in trials studying the treatment of Leukemia, Multiple Myeloma, Malignant Tumors, and Cancer-Solid Tumors and B-Cell Non-Hodgkin's Lymphoma. The antibody product was developed using Medarex's UltiMAb(R) technology and was the first UltiMAb-derived antibody in clinical development by Bristol-Myers Squibb under the December 2003 agreement with Medarex. In December 2008, enrolment was stopped for all urelumab studies following the occurrence of two hepatotoxicity-related deaths. Several years later, the clinical study on Urelumab was restarted. At present, the approval of the monoclonal antibody has not been disclosed in the relevant drug approval agency.
4-1BB (CD137, TNFRSF9) is a costimulatory member of the TNF receptor superfamily that is expressed on a variety of immune cells following activation, including T cells, dendritic cells, and natural killer cells. 4-1BB ligation on T cells triggers a signaling cascade that results in upregulation of antiapoptotic molecules, cytokine secretion, and enhanced effector function. In dysfunctional T cells that have a decreased cytotoxic capacity, 4-1BB ligation demonstrates a potent ability to restore effector functions. On NK cells, 4-1BB signaling can increase antibody-dependent cell-mediated cytotoxicity. Urelumab (BMS-663513, clone 10C7; Bristol-Myers Squibb) is an agonist, non-ligand-blocking, fully human mAb, engineered as an IgG4 to reduce binding to Fc receptors with a hinge mutation (S228P) to improve stability. Agonistic monoclonal antibody, Urelumab, targeting 4-1BB have been developed to harness 4-1BB signaling for cancer immunotherapy. Preclinical results in a variety of induced and spontaneous tumor models suggest that targeting 4-1BB with agonist antibodies can lead to tumor clearance and durable anti-tumor immunity.
Fig.1 Mechanism of action of Urelumab
Table 1. Clinical Projects of Urelumab*
NCT ID | Status | Conditions | Lead Sponsor | Update Time |
NCT02253992 | Recruiting | Acute Lymphoid Leukemia, Acute Lymphoid Leukemia | Bristol-Myers Squibb | October 1, 2014 |
NCT02845323 | Recruiting | Urothelial Carcinoma, Bladder Cancer | Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | July 27, 2016 |
NCT02534506 | Recruiting | Malignant Tumors | Bristol-Myers Squibb | August 27, 2015 |
NCT02658981 | Recruiting | Glioblastoma, Glioblastoma, Recurrent Brain Neoplasm | Sidney Kimmel Comprehensive Cancer Center at Johns Hopkinsr | January 20, 2016 |
NCT03431948 | Recruiting | Cancer | University of Chicago | February 13, 2018 |
NCT02652455 | Active, not recruiting | Melanoma (Skin), Skin Cancer | H. Lee Moffitt Cancer Center and Research Institute | January 11, 2016 |
Reference
* The table was excerpted from the following website
https://clinicaltrials.gov/ct2/results?term=Urelumab
For research use only. Not intended for any clinical use.
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