T-cell antigen CD7 (CD7) (CD7)

T-cell antigen CD7 is a 40 kDa transmembrane glycoprotein and a member of the immunoglobulin superfamily, expressed primarily on thymocytes, mature T-cells, and natural killer (NK) cells. It acts as an early marker of T-cell lineage commitment and functions as a costimulatory molecule during T-cell activation, promoting the production of cytokines like interleukin-2 and interferon-gamma. In clinical oncology, CD7 is a critical marker as it is expressed in over 95% of cases of T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LBL). It is also aberrantly expressed in approximately 30% of acute myeloid leukemia (AML) cases, where its presence is often associated with a poor prognosis. Consequently, CD7 is a major target for various immunotherapies, including chimeric antigen receptor (CAR) T-cell therapies, antibody-drug conjugates (ADCs), and immunotoxins. A primary challenge in CD7-targeted CAR-T therapy is fratricide, where the engineered T-cells target and kill each other due to their own CD7 expression. Current research focuses on mitigating this issue using gene-editing tools to delete CD7 from the CAR-T cells, thereby enhancing their therapeutic efficacy and persistence. Beyond oncology, CD7 has also been explored as a target in autoimmune conditions like systemic sclerosis due to its role in T-cell mediated pathology.

Other names

GP40LEU-9TP41p41 proteinTp40T-cell surface antigen CD7CD7 molecule

Drugs targeting CD7 primarily act through selective depletion of CD7-positive malignant cells. Chimeric antigen receptor (CAR) T-cells engineered to recognize CD7 induce direct cytotoxic killing and apoptosis of leukemia and lymphoma cells. Antibody-drug conjugates (ADCs) and immunotoxins utilize CD7-specific antibodies or nanobodies to deliver lethal payloads, such as topoisomerase inhibitors or bacterial toxins, specifically to cells expressing the antigen. Additionally, experimental antagonists may function by blocking costimulatory signaling between CD7 and its ligands, such as SECTM1, to modulate or suppress unwanted immune responses.