CISH-inactivated tumor-infiltrating lymphocytes

CISH-inactivated tumor-infiltrating lymphocytes is an investigational autologous cell therapy developed by Intima Bioscience for the treatment of metastatic gastrointestinal epithelial cancers. The therapy involves harvesting tumor-infiltrating lymphocytes (TILs) from a patient's tumor and genetically modifying them using CRISPR/Cas9 technology to knock out the *CISH* (cytokine-inducible SH2-containing protein) gene. CISH is an intracellular immune checkpoint that negatively regulates T-cell receptor (TCR) signaling by binding to PLC-γ1, thereby dampening the recognition of cancer neoantigens. By inactivating this checkpoint, the modified TILs exhibit enhanced anti-tumor activity and improved recognition of traditionally 'undruggable' intracellular targets. The treatment protocol typically includes non-myeloablative lymphodepleting chemotherapy followed by the infusion of the engineered TILs and high-dose aldesleukin (IL-2) to support T-cell expansion and persistence.

Other names

CISH-knockout TILsCRISPR-edited CISH-knockout TILsCISH-inactivated TIL