Produktbeschreibung
The recombinant DTA-1-CP028 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 IgG2a, kappa. Published studies have shown engagement of murine Fc gamma receptors (FcgammaRs) is critical for the antitumor effects of antibodies targeting GITR, including DTA-1. Published studies have also demonstrated 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-CP028 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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