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CISH checkpoint inhibitor
- Development stage
- Unknown
- Lead developer
- Intima Bioscience
- Modality
- CRISPR-Cas9 → CRISPR Systems → Programmable Nucleases → Gene Editing → Gene Therapies, Cell Therapies, Small Molecules
- Administration
- Intravenous, Oral
01
Overview
CISH checkpoint inhibitor refers to Intima Bioscience's therapeutic program targeting cytokine-inducible SH2-containing protein (CISH), an intracellular immune checkpoint and negative regulator of T-cell receptor (TCR) signaling. CISH acts by targeting PLC-gamma-1 for proteasomal degradation, thereby suppressing T-cell activation and expansion. The program includes two primary modalities: an autologous, CRISPR-Cas9-engineered CISH-knockout tumor-infiltrating lymphocyte (TIL) cell therapy, and an oral small molecule (molecular glue) checkpoint inhibitor. The CISH-knockout TIL therapy is in Phase 1/2 clinical development (NCT04426669, NCT05566223) for the treatment of metastatic gastrointestinal epithelial cancers (including colorectal, pancreatic, gallbladder, esophageal, and gastric cancers) and non-small cell lung cancer. Preclinical development is also underway for the oral small molecule CISH inhibitor.
- Other names
- CISH inactivated TILsCISH inactivated tumor infiltrating lymphocyte cell therapyCISH inhibitorCISH-knockout TIL therapyCISH-targeting program
02
Targets
CISH (Cytokine-inducible SH2-containing protein)PLCG1 (Phospholipase C gamma 1)
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