Interleukin-7 receptor alpha (IL-7RA) (IL-7RA)

Interleukin-7 receptor alpha (IL-7RA), also known as CD127, is a type I cytokine receptor that is essential for lymphocyte development and the maintenance of the peripheral T-cell pool (UniProt P16871). The engineered constitutively active C7R variant is a synthetic modification, often involving a cysteine insertion in the extracellular juxtamembrane domain, which facilitates ligand-independent homodimerization and continuous signaling through the JAK/STAT5 pathway (Shum et al., 2017, Cancer Res). This engineering strategy is primarily employed in chimeric antigen receptor (CAR) T-cell therapy to enhance cell persistence and metabolic fitness within the immunosuppressive tumor microenvironment, where endogenous IL-7 is often limited (PMID: 28416543). By providing a cell-intrinsic survival signal, C7R-modified T cells demonstrate superior anti-tumor activity against various malignancies, including solid tumors like neuroblastoma and glioblastoma. However, the use of a constitutively active growth signal necessitates rigorous safety monitoring due to the theoretical risk of malignant transformation of the engineered T cells and increased potential for immune-related toxicities.

Other names

CD127C7RConstitutively active IL-7 receptorIL7RInterleukin-7 receptor subunit alpha

Ligand-independent dimerization leading to constitutive JAK1/STAT5 signaling activation (PMID: 28416543).