autologous CXCR2-modified CD70 CAR T cells

A preparation composed of ex-vivo expanded CXC chemokine receptor 2 (CXCR2) modified patient-derived activated CD70 (CD27 ligand; tumor necrosis factor superfamily member 7; TNFSF7) chimeric antigen receptor (CAR) (8R-70CAR) T cells, with potential immunostimulating and antineoplastic activities. Upon admi nistration of the autologous CXCR2-modified CD70 CAR Tcells, the anti-CD70-CARs on the T cell surfaces target and bind to the CD70 antigen on tumor cell surfaces. This induces a cytotoxic T-lymphocyte (CTL)-mediated immune response against CD70-expressing tumor cells. CD70, a cytokine belonging to the tumor necrosis factor 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. CXCR2, a transmembrane protein also known as interleukin (IL)-8 receptor B (IL-8RB), plays a key role in inflammation and cancer progression. Certain CXCR2 ligands, such as CXCL1 and CXCL8 (IL-8), are expressed by tumor cells. CXCR2-modified CARs enhance intratumoral T-cell trafficking toward tumor cells and promotes persistence of T cells. This may enhance the T-cell-mediated immune response against the CD70-expressing tumor cells.