RecombiMAb anti-mouse TNFα

About RecombiMAb anti-mouse TNFα

The XT3.11-CP074 monoclonal antibody is a recombinant, chimeric version of the original XT3.11 antibody. The variable domain sequences are identical but the constant region sequences have been switched from rat IgG1 to murine IgG2a, kappa for use in murine models. Antibody-dependent cellular cytotoxicity (ADCC) is a contributing mechanism of action of anti-TNF antibodies, since anti-TNF antibodies have been confirmed to induce cytotoxic effects on TNF-producing cells via ADCC and complement-dependent cytotoxicity (CDC). Murine IgG2a mediates ADCC primarily through its high-affinity binding to the mFcγRIV receptor, a key effector mechanism in the mouse immune system for targeting diseased or infected cells. In contrast to other isotypes, mIgG2a demonstrates strong effector functions due to this potent interaction with mFcγRIV, which is functionally like the FcγRIIIa receptor involved in human ADCC. Species-matched chimeric antibodies result in less immunogenicity and formation of anti-drug antibodies (ADAs) than xenogenic antibodies in animal models. The highly controlled sequence and lack of genetic drift in recombinant antibodies provide more reliable and reproducible results over hybridoma derived antibodies. The XT3.11-CP074 monoclonal antibody reacts with mouse TNFα (tumor necrosis factor-alpha) a multifunctional proinflammatory cytokine. TNFα exists as a soluble 17 kDa monomer, which forms homotrimers in circulation or as a 26 kDa membrane-bound form. TNFα belongs to the TNF superfamily of cytokines and signals through its two receptors, TNFR1 and TNFR2 which can be activated by both the soluble trimeric and membrane-bound and forms of TNFα. TNFα is primarily produced by macrophages in response to foreign antigens such as bacteria (lipopolysaccharides), viruses, and parasites as well as mitogens and other cytokines but can also be expressed by monocytes, neutrophils, NK cells, CD4 T cells and some specialized dendritic cells. TNFα is known to play key roles in a wide spectrum of biological processes including immunoregulation, cell proliferation, differentiation, apoptosis, antitumor activity, inflammation, anorexia, cachexia, septic shock, hematopoiesis, and viral replication. TNFα dysregulation has been implicated in a variety of diseases, including autoimmune diseases, insulin resistance, and cancer. Mouse and human TNFα share 79% amino acid sequence identity however, mouse TNFα is glycosylated while human TNFα is not. TNFα knockout animals display defects in response to bacterial infection, characterized by defects in forming organized follicular dendritic cell networks and germinal centers with a lack of primary B cell follicles.