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- W2548608582 abstract "Abstract CD70 (CD27L) is a member of the tumor necrosis factor superfamily that is predominantly expressed on activated lymphocytes and is important for generation of B and T memory and effector responses. High levels of CD70 are also found on chronically activated T cells and lymphocytes in patients with autoimmune disorders. Blockade of CD70 interaction with its receptor has been shown to inhibit the onset of experimental autoimmune encephalomyelitis and cardiac allograft rejection in mice. We have engineered a humanized anti-CD70, SGN-70, that mediates Fc-dependent antibody effector functions and blocks binding of CD70 to its receptor. In this report we show that SGN-70 inhibits co-stimulation of T lymphocytes, and selectively depletes CD70+ activated T cells. Depletion of antigen-specific T cells by SGN-70 was demonstrated using CD8+ T cells specific for a peptide (M58-66) derived from the influenza A matrix protein M1. Stimulation of peripheral blood mononuclear cells with the M1 peptide markedly induced CD70 expression within a discrete expanding of M1 peptide-specific CD8+Vβ17+ T cell subset. Treatment of peptide-stimulated cultures with SGN-70 (0.01–1 μg/mL) decreased the number of CD70+CD8+Vβ17+ cells by >80%. This depletion was dependent on the activity of CD16+ cells within the culture since blocking CD16 completely eliminated the depleting effect of SGN-70. Non-activated Vβ17 negative cells were not affected by SGN-70 and were functionally equivalent to untreated control cultures in subsequent response to mitogenic re-stimulation. Together, these data demonstrate the capacity of SGN-70 to selectively target activated cells and its potential to limit expansion of antigen-specific T lymphocytes. Thus, SGN-70 may have therapeutic potential to target T cell-mediated autoimmune and inflammatory diseases." @default.
- W2548608582 created "2016-11-11" @default.
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- W2548608582 date "2006-11-16" @default.
- W2548608582 modified "2023-09-30" @default.
- W2548608582 title "Targeted Depletion and Inhibition of Activated T Lymphocytes with SGN-70, a Humanized Antibody Specific for the Activation Antigen CD70." @default.
- W2548608582 doi "https://doi.org/10.1182/blood.v108.11.1728.1728" @default.
- W2548608582 hasPublicationYear "2006" @default.
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