CD27 is a transmembrane glycoprotein belonging to the tumor necrosis factor receptor (TNFR) superfamily, primarily expressed on T cells, B cells, and natural killer (NK) cells. It plays a critical role in regulating immune cell activation, differentiation, and survival. CD27 interacts with its ligand CD70. a transiently expressed protein on activated immune cells, to mediate co-stimulatory signals essential for T-cell expansion, memory formation, and B-cell antibody production. Dysregulation of the CD27-CD70 axis is implicated in autoimmune diseases, immunodeficiency, and cancer.
CD27-targeting antibodies have emerged as promising therapeutic tools. Agonistic anti-CD27 antibodies can enhance T-cell-mediated immunity by mimicking CD70 signaling, potentially augmenting antitumor responses. Conversely, antagonistic antibodies blocking CD27-CD70 interaction may suppress excessive immune activation in autoimmune conditions. In oncology, CD27 agonists are explored in clinical trials, often combined with checkpoint inhibitors, to boost effector T-cell activity against tumors. Notably, varlilumab, a humanized anti-CD27 monoclonal antibody, has shown tolerability and immune-modulating effects in early-phase trials for solid and hematologic malignancies. However, challenges remain, including balancing efficacy with potential toxicity (e.g., cytokine release syndrome) and understanding context-dependent roles of CD27 in tumor microenvironments. Research continues to optimize CD27 antibody design and therapeutic strategies across immune-related diseases.