TNF-α Chimeric Mouse-Human Monoclonal Antibody (Clone CDP 571)

TNF-α is a cytokine and member of the TNF/TNF receptor (TNFR) cytokine superfamily.¹ TNF-α is produced as a 233-amino acid transmembrane precursor protein from which mature, soluble TNF-α is formed by proteolysis.² Soluble TNF-α is a 157-amino acid polypeptide, cleaved from the precursor protein on the extracellular side of the membrane, that forms bell-shaped homotrimers with the C-termini at the base, each containing three receptor interaction sites.³ It is primarily produced by activated macrophages but can also be produced by a variety of other cells, such as T cells, natural killer cells, and osteoblasts.^3,4 TNF-α binds to and activates its receptors, TNFR1 and TNFR2, which are associated with intracellular protein complexes that activate caspases to induce cell death, induce p38 MAPK signaling, and initiate NF-κB or AP-1-mediated transcription of immune and inflammatory mediators.⁵ TNF-α promotes inflammation partly by inducing endothelial cells to express adhesion molecules, COX enzymes, and pro-coagulant factors.⁴ Exogenous TNF-α induces death of cancer cells in vitro, as well as disrupts tumor vascularization and induces tumor necrosis in vivo, but it has tumor-promoting properties when produced in the cancer microenvironment.^1,6 In contrast, it plays a role in resistance to infection, with mice lacking Tnf having an increased susceptibility to certain microbial infections but lacking resistance to leishmania.⁵ Tnf knockout mice are also resistant to certain types of cancer, including chemically induced skin carcinogenesis.¹ TNF-α increases lung metastases in a mouse model of fibrosarcoma, an effect that can be reduced by an anti-TNF-α antibody. Mice overexpressing Tnf develop an arthritis similar to rheumatoid arthritis in humans.⁷ TNF-α is produced in the inflamed tissues of patients with inflammatory diseases such as rheumatoid arthritis and neutralizing antibodies to TNF-α reduce the levels of TNF-α in vitro and in mouse models of the disease.⁴ Cayman’s TNF-α Chimeric Mouse-Human Monoclonal Antibody (Clone CDP 571) was produced recombinantly from the original CDP 571 antibody sequence and can be used for ELISA and as a neutralizing antibody. The CDP 571 antibody was generated by fusing human IgG4 constant domains to the antigen-binding domain of a mouse anti-human TNF-α monoclonal antibody.⁸

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