A novel TNFR2 agonist antibody expands highly potent regulatory T cells

Regulatory T cells (Treg cells) restrict immune system activity, such as in response to self-antigens, and are switched on by tumor necrosis factor receptor 2 (TNFR2). Therapeutic activation of TNFR2, thereby expanding Treg cells and suppressing immune activity, may be beneficial to patients with various inflammatory diseases. Here, we characterized a new human TNFR2-directed antibody agonist isolated from mice. We found that the antibody agonist expanded the number of Treg cells within cultures of primary human CD4+ T cells from healthy donors and patients with type 1 diabetes or Sézary syndrome. These Treg cells had increased metabolic gene expression and intracellular itaconate concentrations, characteristics associated with maximally suppressive, anti-inflammatory Treg cells. Furthermore, antibody-expanded Treg cells repressed the activity of primary human CD8+ effector T cells (Teff cells). Epitope mapping suggested that the antibody bound to TNFR2 through a natural cross-linking s..., Isolated human CD4 cells were cultured for 10 hours in the presence of IL2 only or IL-2 and agonist antibody. The cells were then washed with PBS, total RNA isolated and processed for RNAseq on NextSeq flow cells.
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