autologous PD-1-knockout tumor-infiltrating lymphocytes IOV-4001

A preparation of autologous tumor-infiltrating lymphocytes (TILs) where the programmed cell death protein 1 (PD-1; PDCD1; CD279; programmed death-1) gene has been disrupted using transcription activator-like effector nuclease (TALEN), with potential immunomodulating and antineoplastic activities. The autologous TILs are isolated from an autologous tumor sample, expanded ex-vivo and genetically modified to inactivate PD-1. Upon administration, the autologous PD-1-knockout TILs IOV-4001 induce a T-cell-mediated immune response against tumor cells. Expression of PD-1, an inhibitory receptor expressed on activated T cells, plays a key role in cytotoxic T-lymphocyte (CTL) suppression, T-cell exhaustion and CTL apoptosis. PD-1 knockout may abrogate T-cell exhaustion and increase T-cell activity and cytotoxicity.