Fig. 2: Compound screening in mice identified SAR’336, an IL-2 variant pegylated at residue H16, which significantly expanded Treg populations compared to other compounds.
From: A CD25-biased interleukin-2 for autoimmune therapy engineered via a semi-synthetic organism
A single subcutaneous dose (~0.9 mg/kg) of the indicated variant was administered to C57BL/6 mice. Flow cytometry was used to quantitate Treg (CD4 + CD25+ FoxP3 +), CD8 T and NK cell expansion in peripheral blood. Shown in the plot is the (a) frequency and (b) maximum fold Treg expansion over vehicle for each compound (mean of three individual animals ± SEM); (c) Percentage and fold change of peripheral blood cells that were Treg, CD8 and NK cells is plotted as a function of time post dose (mean of three individual animals, ±SEM). Azk azide-containing non-canonical amino acid N6-(2-azidoethoxy)-carbonyl-L-lysine, CD4 cluster of differentiation 4, CD8 cluster of differentiation 8, CD25 cluster of differentiation 25, FoxP3 forkhead box protein 3, H16-Azk IL-2 variant with residue H16 replaced with the non-canonical amino acid Azk, IL-2 interleukin-2, NK natural killer cell, SEM standard error of mean, Treg regulatory T cell, WBC white blood cell.
