Cluster of differentiation 70 (CD70) (CD70)

Cluster of differentiation 70 (CD70), also known as TNFSF7, is a type II transmembrane protein and a member of the tumor necrosis factor (TNF) superfamily [1, 2]. It serves as the ligand for the CD27 receptor, and their interaction provides critical co-stimulatory signals for the activation, proliferation, and survival of T and B cells [1, 8]. While its expression is transient and tightly regulated in healthy tissues—limited primarily to activated lymphocytes and mature dendritic cells—CD70 is aberrantly and constitutively overexpressed in a wide range of hematologic malignancies and solid tumors [2, 4, 13]. In the tumor microenvironment, CD70 promotes immune evasion by inducing T-cell exhaustion and expanding regulatory T cells, while also directly driving tumor cell proliferation through autocrine signaling [9, 10]. Consequently, CD70 has emerged as a highly attractive therapeutic target, with various modalities under development, including monoclonal antibodies, antibody-drug conjugates (ADCs), and chimeric antigen receptor (CAR) T-cell therapies [2, 7, 13]. These agents aim to eliminate tumor cells through mechanisms such as antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), and direct T-cell-mediated killing [5, 6]. However, challenges such as potential 'fratricide' of CAR-T cells and on-target off-tumor effects on activated immune cells remain key considerations in clinical development [2, 17].

Other names

TNFSF7CD27LCD27LGTumor necrosis factor ligand superfamily member 7CD27 ligand

Antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), complement-dependent cytotoxicity (CDC), CAR-T cell-mediated lysis, and inhibition of CD70-CD27 interaction to disrupt survival signaling and immune evasion.