CD70. a member of the tumor necrosis factor (TNF) superfamily, is the ligand for CD27 and plays a critical role in regulating immune cell activation and survival. It is transiently expressed on activated T and B lymphocytes, dendritic cells, and certain antigen-presenting cells under normal physiological conditions. However, CD70 is aberrantly overexpressed in various malignancies, including hematological cancers (e.g., lymphomas, multiple myeloma) and solid tumors (e.g., renal cell carcinoma, glioblastoma), as well as in autoimmune disorders. This overexpression is often linked to immune evasion, tumor progression, and poor prognosis.
CD70-targeting antibodies are designed to block CD70-CD27 signaling, which disrupts pro-survival pathways in cancer cells and modulates immune responses. These antibodies may also exert therapeutic effects via antibody-dependent cellular cytotoxicity (ADCC) or complement-dependent cytotoxicity (CDC). Additionally, CD70 antibodies are being explored as components of antibody-drug conjugates (ADCs) or bispecific antibodies to enhance tumor-specific targeting.
Current clinical development includes anti-CD70 agents like cusatuzumab (for acute myeloid leukemia) and ARGX-110 (for T-cell lymphomas), with ongoing trials evaluating safety and efficacy. Challenges include managing on-target off-tumor toxicity due to CD27 expression on normal lymphocytes. Nonetheless, CD70 remains a promising therapeutic target, particularly for cancers with limited treatment options.