Table 2. Comparison of unaltered and next-generation gamma-chain cytokines.
| Variables | Half-life | Dosing | Safety | CD8 T-cell/NK cell increase | |
|---|---|---|---|---|---|
| IL-2 | |||||
| Unaltered (Aldesleukin) | 13–85 min | Daily | Low-dose expands Tregs | N/A | |
| HD has life-threatening toxicities | |||||
| Next-Gen (ALKS 4230; FAP-IL-2v; GI-101; hu14.18-IL2; L19-IL2; NKTR-214; RO72284755; THOR-707) | Up to 10–17 h | Q2W–Q3W | Decreased Treg engagement and increased potency allow for lower doses and a better safety profile | Up to 3X CD8 T-cells | |
| Up to 8X NK cells | |||||
| IL-7 | |||||
| Unaltered (CYT-107) | 6–10 h (unglycosylated) | Q1W–Q2W | Good safety profile (no MTD reached) | Up to 2X CD8 T-cells | |
| 9–35 h (glycosylated) | |||||
| Next-Gen (NT-I7/GX-I7 (efineptakin alfa)) | 33–147 h | Q3W–Q12W | Good safety profile (no MTD reached) | Up to 4X CD8 T-cells (preferential TSCM expansion) | |
| IL-15 | |||||
| Unaltered (rhIL-15) | 2.5 h | Daily | Marked elevation of inflammatory cytokines with i.v. injection, better safety profile when administered s.c. | Up to 1.5–2X CD8 T-cells | |
| Up to 2–3X NK cells | |||||
| Next-Gen (N-803; NKTR-255) | Up to 30 h | Q1W–Q4W | Well tolerated | Up to 2.5X NK cells | |
| IL-21 | |||||
| Unaltered (rIL-21) | 3 h | Daily | Serious dose-limiting toxicities | Up to 2.5X NK cells | |
| Next-Gen | N/A | N/A | N/A | N/A | |
N/A, not applicable.