Interleukin-2 receptor on PD-1-positive T cells (IL-2R on PD-1+ T cells)

The Interleukin-2 receptor (IL-2R) on PD-1-positive T cells is a precision immunotherapy target designed to localize the potent activity of IL-2 to specific immune cell subsets (Waldmann, 2006, Nature Reviews Immunology). IL-2 is a critical cytokine for T cell expansion, but its systemic use is limited by severe toxicity and the unintended stimulation of regulatory T cells (Tregs) (Arenas-Ramirez et al., 2015, Science Translational Medicine). By targeting the IL-2R specifically on cells expressing the Programmed Cell Death Protein 1 (PD-1), such as exhausted tumor-infiltrating lymphocytes (TILs), therapeutic agents can selectively reinvigorate the anti-tumor immune response (Codarri Deak et al., 2022, Nature Communications). This is typically achieved using bispecific fusion proteins, such as RO7284755 (PD1-IL2v), which combine a PD-1-binding domain with a modified IL-2 variant that has reduced affinity for the IL-2Rα (CD25) subunit (Roche, 2022, AACR Annual Meeting). This selectivity ensures that the IL-2 signal is delivered to effector T cells rather than Tregs or vascular endothelial cells, potentially improving the therapeutic index (Innovent Biologics, 2023, IBI363 Data). Clinical development of drugs targeting this complex is primarily focused on treating advanced solid tumors that are resistant to standard checkpoint inhibitors (ClinicalTrials.gov, NCT04303858).

Other names

PD-1-targeted IL-2 receptorPD1-IL2v targetIL-2R on exhausted T cellsIL-2R on PD-1+ tumor-infiltrating lymphocytes

Selective delivery of IL-2 signaling to PD-1-expressing effector T cells via a bispecific antibody-cytokine fusion protein, typically utilizing an IL-2 variant (IL-2v) with abolished CD25 binding to avoid regulatory T cell activation and systemic toxicity.