Definition

A preparation of autologous T lymphocytes that are genetically engineered to contain a dual-targeted chimeric antigen receptor (CAR), which includes a trimeric form of the natural protein a proliferation-inducing ligand (APRIL; TNFSF13), that targets the tumor-associated antigens (TAAs) B-cell maturation antigen (BCMA; TNFRSF17) and transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI; TNFRSF13B), with potential immunomodulating and antineoplastic activities. Upon administration, the autologous BCMA/TACI-targeted trimeric APRIL-based CAR T cells bind to BCMA and TACI expressed on tumor cells and induce selective cytotoxicity in those cells. BCMA and TACI, receptors for both APRIL and B-cell activating factor (BAFF), are members of the tumor necrosis factor receptor superfamily (TNFRSF). They are both found on the surfaces of plasma cells, overexpressed on malignant plasma cells and play key roles in plasma cell proliferation and survival. The incorporation of the trimeric, natural conformation of APRIL into the CAR enhances the binding to BCMA and TACI compared with the monomeric form of APRIL.