Tumor necrosis factor ligand superfamily member 7 (CD70) (CD70)

CD70 (Tumor necrosis factor ligand superfamily member 7) is a type II transmembrane protein that serves as the sole ligand for the CD27 receptor [4, 11]. Under physiological conditions, its expression is transient and highly restricted to activated T and B lymphocytes, mature dendritic cells, and natural killer cells, where it plays a critical role in regulating immune responses by promoting T-cell expansion, differentiation, and survival [1, 4, 12]. However, CD70 is aberrantly and constitutively overexpressed in a wide range of malignancies, including renal cell carcinoma, non-Hodgkin lymphoma, and multiple myeloma, as well as in certain autoimmune conditions like systemic lupus erythematosus [1, 2, 3, 13]. In the tumor microenvironment, the CD70-CD27 axis facilitates immune evasion by inducing apoptosis of tumor-infiltrating lymphocytes and promoting the expansion of regulatory T cells [5, 6, 18]. Due to its high tumor-to-normal tissue expression ratio, CD70 has become a prominent therapeutic target for monoclonal antibodies, antibody-drug conjugates (ADCs), and chimeric antigen receptor (CAR) T-cell therapies [2, 3, 9, 14]. Clinical development of these agents, such as cusatuzumab and CTX130, aims to leverage mechanisms like antibody-dependent cellular cytotoxicity (ADCC) and direct cytotoxic delivery to eradicate CD70-positive malignant cells [2, 9, 10]. Despite its potential, therapeutic challenges include managing on-target off-tumor toxicity due to transient expression on normal activated immune cells and preventing fratricide in CAR-T cell products [2, 13].

Other names

CD27 ligandCD27LCD27LGTNFSF7CD70 antigenCluster of differentiation 70

Antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), antibody-drug conjugate (ADC) mediated delivery of cytotoxic payloads, and chimeric antigen receptor (CAR) T-cell or NK-cell mediated tumor lysis.