IL-2 receptor subunits CD25 (IL2RA) and CD122 (IL2RB)

Class

Pegylated engineered IL-2 variant (CD25/CD122-selective partial agonist)

Pathway

Selective activation of antigen-experienced effector T-cells without engaging NK/naive T-cells, avoiding vascular leak syndrome

CD25 (IL2RA) and CD122 (IL2RB) are two of the three protein chains that make up the interleukin-2 receptor, the third being the common gamma chain (CD132) shared by several cytokine receptors. Native interleukin-2 (IL-2) is a T-cell growth factor: when it engages the full three-chain receptor, it drives proliferation and functional activation of T lymphocytes, and at lower receptor density it also signals through CD122 and CD132 alone on natural killer (NK) cells and memory T cells. This dual signaling capacity is therapeutically attractive in oncology, where expanding tumor-reactive effector T cells can enhance anti-tumor immunity, but native IL-2 also activates NK cells and vascular endothelium, producing capillary leakage and hypotension that limit dosing. Engineered IL-2 variants designed to act selectively through the CD25/CD122 combination aim to preferentially engage antigen-experienced effector T cells, which display abundant CD25, while sparing NK cells and naive T cells that rely mainly on CD122/CD132 signaling. This selectivity is intended to preserve therapeutic T-cell expansion while reducing the systemic toxicity historically associated with less selective IL-2 therapy, making the mechanism broadly relevant to cancer immunotherapy and, in principle, to immune-modulation strategies more generally.