CD70 is a cell surface protein belonging to the tumor necrosis factor (TNF) superfamily, primarily expressed on activated immune cells such as T cells, B cells, and dendritic cells. It interacts with its receptor CD27. a costimulatory molecule critical for T-cell activation, B-cell differentiation, and immune regulation. While CD70-CD27 signaling supports normal immune responses, dysregulated CD70 expression is implicated in pathological conditions, including cancers (e.g., renal cell carcinoma, lymphomas) and autoimmune diseases.
CD70-targeted antibodies have emerged as therapeutic tools to modulate this pathway. In oncology, anti-CD70 antibodies aim to block pro-survival signaling in CD70-positive tumors or deliver cytotoxic payloads via antibody-drug conjugates (ADCs). Some antibodies also engage Fc-mediated effector functions, such as antibody-dependent cellular cytotoxicity (ADCC), to eliminate malignant cells. In autoimmune contexts, inhibiting CD70-CD27 interactions may suppress overactive immune responses.
Notable examples include MDX-1203 (anti-CD70 ADC) and cusatuzumab (anti-CD70 mAb), which have undergone clinical trials for hematologic malignancies. Challenges include managing on-target toxicity due to CD27’s broad immune role and optimizing selectivity for diseased tissues. Ongoing research explores bispecific formats and combination therapies to enhance efficacy. Overall, CD70 antibodies represent a promising, albeit complex, avenue for precision immunotherapy.