TNFSF4 Chimeric Monoclonal Antibody (Clone R4930 (Oxelumab))

TNF ligand superfamily member 4 (TNFSF4), also known as OX40L, is a type II transmembrane protein and the cognate ligand of the T cell co-stimulatory TNF receptor TNFRSF4, also known as OX40.^1,2 TNFSF4 assembles into trimers, with each monomer possessing an approximately 132-amino acid extracellular domain composed of a TNF homology domain followed by a C-terminal extension. It is upregulated in antigen-presenting cells, including B cells, macrophages, and dendritic cells, in response to antigen presentation, and is also expressed in mast cells, activated T cells, and certain endothelial cells.² Binding of a TNFSF4 trimer to three TNFRSF4 monomers promotes T cell survival and memory, as well as an effector T cell phenotype, enhances cell mobility, and increases the production of effector cytokines. Polymorphisms in TNFSF4 are associated with susceptibility to systemic lupus erythematosus (SLE) and systemic sclerosis.^3,4 Cayman’s TNFSF4 Chimeric Monoclonal Antibody (Clone R4930 (Oxelumab)) was recombinantly generated based on the sequence of the original humanized anti-TNFSF4 antibody and can be used for flow cytometry (FC). The humanized anti-TNFSF4 antibody was generated by immunizing HCo12 human IgG transgenic mice with alternating administration of recombinant human TNFSF4 and human TNSF4-expressing cells.^5,6,7

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1. Compaan, D.M., and Hymowitz, S.G. The crystal structure of the costimulatory OX40-OX40L complex. Structure 14(8), 1321-1330 (2006).

2. Webb, G.J., Hirschfield, G.M., and Lane, P.J.L. OX40, OX40L and autoimmunity: A comprehensive review. Clin. Rev. Allergy Immunol. 50(3), 312-332 (2016).

3. Lee, Y.H., and Song, G.G. Associations between TNFSF4 and TRAF1-C₅ gene polymorphisms and systemic lupus erythematosus: A meta-analysis. Hum. Immunol. 73(10), 1050-1054 (2012).

4. Gourh, P., Arnett, F.C., Tan, F.K., et al. Association of TNFSF4 (OX40L) polymorphisms with susceptibility to systemic sclerosis. Ann. Rheum. Dis. 69(3), 550-555 (2010).

5. Seshasayee, D., Lee, W.P., Zhou, M., et al. In vivo blockade of OX40 ligand inhibits thymic stromal lymphopoietin driven atopic inflammation. J. Clin. Invest. 117(12), 3868-3878 (2007).

6. Gauvreau, G.M., Boulet, L.-P., Cockroft, D.W., et al. OX40L blockade and allergen-induced airway responses in subjects with mild asthma. Clin. Exp. Allergy 44(1), 29-37 (2014).

7. Jodeleit, H., Winkelmann , P., Caesar, J., et al. Head-to-head study of oxelumab and adalimumab in a mouse model of ulcerative colitis based on NOD/Scid IL2Rγnull mice reconstituted with human peripheral blood mononuclear cells. Dis. Model. Mech. 14(1), dmm046995 (2021).