Interleukin-2 receptor subunit alpha (CD25) and Programmed cell death protein 1 (PD-1) (IL-2Rα/PD-1)

The target "IL-2 receptor α on PD-1+ cells" refers to a dual-targeting therapeutic strategy involving the Interleukin-2 receptor subunit alpha (IL-2Rα, also known as CD25) and the Programmed cell death protein 1 (PD-1, also known as CD279). This approach typically utilizes bispecific antibodies or fusion proteins, such as IBI363, designed to selectively deliver IL-2 signaling to PD-1-expressing cells, which are often exhausted or activated tumor-infiltrating lymphocytes (TILs) [1, 4]. By incorporating an IL-2Rα-biased component, these therapies aim to enhance the potency of IL-2 signaling on target cells while using the PD-1 arm to ensure specificity for the tumor microenvironment, thereby reducing the systemic toxicity (like vascular leak syndrome) associated with high-dose IL-2 [1]. IL-2Rα is a high-affinity receptor subunit primarily expressed on activated T cells and regulatory T cells (Tregs), while PD-1 is a key immune checkpoint receptor that limits T-cell activity in chronic infections and cancer [2, 3]. This dual-targeting mechanism is primarily investigated in oncology to reinvigorate anti-tumor immunity and overcome resistance to standard checkpoint inhibitors by selectively expanding effector T cells over Tregs. It represents a significant advancement in the development of "next-generation" cytokines designed for improved safety and efficacy in treating various solid tumors and lymphomas.

Other names

CD25/PD-1IL2RA/PDCD1PD-1-targeted IL-2Rα-biased cytokineCD25 and CD279

Bispecific binding to PD-1 and IL-2Rα to selectively deliver IL-2 signaling to PD-1-expressing T cells.