Interleukin-2 receptor complex (IL-2R) on Programmed cell death protein 1 positive (PD-1+) T cell (IL-2R on PD-1+ T cell)

The Interleukin-2 receptor (IL-2R) complex on PD-1-positive T cells is a specialized therapeutic target designed to localize the potent immunostimulatory effects of IL-2 to tumor-reactive lymphocytes [3, 6]. In many cancers, effector T cells within the tumor microenvironment express high levels of the programmed cell death protein 1 (PD-1) and enter a state of exhaustion [7, 13]. Drugs like TEV-56278 utilize a 'cis-targeting' strategy, where an antibody-cytokine fusion protein binds to PD-1 and simultaneously engages the IL-2R on the same cell surface [10, 11]. This approach employs an attenuated IL-2 variant that has reduced affinity for the receptor, ensuring that signaling only occurs when the molecule is tethered to the cell via PD-1 [3, 14]. By focusing IL-2 activity on PD-1-positive exhausted T cells, this target allows for the selective reinvigoration of anti-tumor immunity while avoiding the systemic toxicities, such as vascular leak syndrome, typically associated with high-dose IL-2 therapy [6, 9]. This mechanism also promotes the establishment of durable immune memory and can be combined with standard-of-care PD-1 inhibitors because the targeting antibody does not block the PD-1/PD-L1 interaction [13, 14].

Other names

PD-1-targeted IL-2 receptorIL-2R on exhausted T cellsPD-1/IL-2R complexATTENUKINE targetPD-1 x IL-2R

Cis-targeting of attenuated IL-2 to PD-1-expressing T cells to selectively activate tumor-reactive effector cells while minimizing systemic toxicity.