Definition

A preparation of T lymphocytes that are genetically engineered to express a fourth-generation chimeric antigen receptor (4SCAR) targeting the two tumor-associated antigens (TAAs) CD19 and CD70 (CD27 ligand; tumor necrosis factor superfamily member 7; TNFSF7), with potential immunostimulating and antineoplastic activities. Upon administration, the anti-CD19/anti-CD70 4SCAR-expressing bispecific T cells are directed to and induce selective toxicity in CD19- and CD70-expressing tumor cells. CD19 antigen is a B-cell specific cell surface antigen expressed in all B-cell lineage malignancies. CD70, a cytokine belonging to the tumor necrosis superfamily (TNFSF) and the ligand for the costimulatory receptor CD27, is expressed on the surfaces of various types of cancer cells; its overexpression may play an important role in the evasion of immune surveillance. CD19 and CD70 are expressed at high levels on tumor cells but not at significant levels on normal tissues. Targeting two antigens may protect against antigen escape and may enhance CAR-T cell efficacy.