CISH inactivated TIL + pembrolizumab

CISH inactivated TIL + pembrolizumab is a combination immunotherapy consisting of tumor-infiltrating lymphocytes (TILs) genetically engineered to inactivate the CISH gene (cytokine-inducible SH2-containing protein) and the PD-1 checkpoint inhibitor pembrolizumab. The CISH gene product suppresses T cell receptor (TCR) and cytokine signaling; inactivation via CRISPR/Cas9 increases TIL proliferation, cytokine polyfunctionality, cytolytic activity, and sensitivity to tumor neoantigens[2][3][4]. Pembrolizumab, a monoclonal antibody targeting the PD-1 receptor, blocks external T cell inhibition by the PD-L1/PD-1 axis. The combination aims to maximize both internal (CISH) and external (PD-1) checkpoint blockade, potentially resulting in greater antitumor efficacy than either modality alone[1][2][3]. This approach is under clinical investigation for metastatic solid tumors, including gastrointestinal cancers and non-small cell lung cancer[1][3][6].

Other names

CISH knockout TIL + pembrolizumabCISH KO TIL + pembrolizumab