Product Description
The recombinant DTA-1-CP027 monoclonal antibody is a chimeric version of the original DTA-1 antibody. The variable domain sequences are identical to the original DTA-1 but the constant region sequences have been switched from rat IgG2b, lambda to mouse IgG1, kappa. The DTA-1-CP027 antibody also contains the D265A mutations in the heavy chain Fc fragment rendering it unable to bind to endogenous murine Fcgamma receptors. Published studies demonstrate the original rat DTA-1 antibody can result in anaphylaxis in mice upon repeated intraperitoneal dosing due to the generation of an anti-idiotypic anti-drug Ab immune response. Chimerization of DTA-1 with a murine constant region results in reduced development and severity of anaphylaxis in mice but does not affect T cell agonistic properties or in vivo antitumor efficacy. The DTA-1-CP027 antibody reacts with mouse GITR (glucocorticoid-induced TNFR-related gene), a 66-70 kDa co-stimulatory immune checkpoint molecule belonging to the Tumor Necrosis Factor superfamily (TNFRSF18). GITR is expressed at low levels on resting T lymphocytes and at high levels on regulatory T cells. GITR is upregulated on activated T cells where it provides co-stimulation. GITR is thought to play a key role in dominant immunological self-tolerance maintained by regulatory T cells. Knockout studies in mice suggest the role of this receptor is in the regulation of CD3-driven T cell activation and programmed cell death. The DTA-1 antibody is an agonistic antibody that is commonly used to induce GITR signaling in vivo.
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