Constitutively active interleukin-7 receptor alpha (C7R) (C7R)

The constitutively active interleukin-7 receptor (C7R) is an engineered signaling protein designed to enhance the survival, expansion, and anti-tumor potency of Chimeric Antigen Receptor (CAR) T cells (Shum et al., 2017). In its natural state, the IL-7 receptor (IL-7R) requires the binding of the cytokine IL-7 and the presence of the common gamma chain (γc) to initiate signaling (UniProt P16871). C7R is modified—typically by inserting a cysteine-rich sequence into the extracellular juxtamembrane domain—to facilitate ligand-independent homodimerization of the IL-7Rα chain. This modification triggers continuous activation of the Janus kinase (JAK)/Signal transducer and activator of transcription 5 (STAT5) pathway, providing a steady pro-survival signal that mimics chronic cytokine support. This is particularly beneficial in the immunosuppressive tumor microenvironment, where endogenous IL-7 is often limited, leading to improved CAR-T cell persistence and efficacy against solid and hematologic malignancies (Zhao et al., 2020). However, the permanent activation of growth pathways necessitates rigorous safety monitoring to prevent potential T-cell transformation or excessive systemic inflammation.

Other names

CD127IL7RAInterleukin-7 receptor subunit alphaEngineered IL-7 receptorConstitutively active IL-7R alpha

Ligand-independent homodimerization of the engineered IL-7 receptor alpha chain, leading to constitutive activation of the JAK1/STAT5 signaling pathway and upregulation of anti-apoptotic proteins like BCL-2.