Table 2.
NKTR-358 favors activation of Treg over Tcon as compared with IL-2. PBMCs from cynomolgus monkey and human whole blood were obtained from two healthy female and male donors from each species and stimulated in vitro with at least 12 different concentrations ≈1 log apart of each test item. pSTAT5 MFI on different lymphocyte populations was measured by flow cytometry and used to determine EC50 values. An EC50 was calculated from each donor for each population and averaged. EC50, half maximal effective concentration; MFI, mean fluorescence intensity; PBMC, peripheral blood mononuclear cell; SD, standard deviation; Tcon, conventional T cell; Treg, regulatory T cell.
| pSTAT5 EC50 (mean ± SD), ng/mL |
||||||||
|---|---|---|---|---|---|---|---|---|
| CD3+ T cells | CD4+CD25+ T cells | CD8+ T cells | CD4+CD25+:CD8+ ratio | |||||
| Test material | Monkey PBMCs | Human PBMCs | Monkey PBMCs | Human PBMCs | Monkey PBMCs | Human PBMCs | Monkey PBMCs | Human PBMCs |
| rhIL-2 | 8.87 ± 4.77 | 1.34 ± 0.416 | 0.0166 ± 0.00924 | 0.0198 ± 0.00357 | 12.7 ±7.36 | 6.22 ±2.041 | 0.001 ± 0.001 | 0.003 ± 0.001 |
| NKTR-358 | 4760 ± 2480 | 4020 ± 1410 | 50.5 ± 21.6 | 148 ± 58.3 | 5450 ± 2786 | 4720 ± 2121 | 0.01 ± 0.002 | 0.034 ± 0.017 |
| Ratio NKTR-358/rhIL-2 | 550 ± 100 | 3083 ± 1065 | 4655 ± 4354 | 7229 ± 1985.8 | 441 ± 87.9 | 757 ± 204.9 | – | – |