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CISH-KO iNK cells
- Development stage
- Preclinical
- Lead developer
- Concentra Biosciences
- Modality
- CRISPR-Cas9 → CRISPR Systems → Programmable Nucleases → Gene Editing → Gene Therapies, CAR-NK Cells → Other Engineered Cells → Adoptive Cell Transfer → Cell Therapies, Lymphokine-Activated Killer Cells → Native Immune Cells → Adoptive Cell Transfer → Cell Therapies, iPSCs → Pluripotent Stem Cells → Stem Cell Therapies → Cell Therapies
- Administration
- Intravenous
01
Overview
CISH-KO iNK cells are an allogeneic, off-the-shelf cellular immunotherapy consisting of natural killer (NK) cells derived from induced pluripotent stem cells (iPSCs) that have been genetically modified using CRISPR/Cas9 to knock out the *CISH* (cytokine-inducible SH2-containing protein) gene. The *CISH* gene normally acts as an intracellular checkpoint and negative regulator of interleukin-15 (IL-15) signaling in NK cells; its deletion enhances the metabolic fitness, in vivo persistence, and anti-tumor cytotoxicity of the cells. Developed by Shoreline Biosciences, these engineered cells are designed to treat various hematological malignancies and solid tumors, including acute myeloid leukemia (AML) and ovarian cancer, by overcoming the immunosuppressive tumor microenvironment and resisting cell exhaustion. The therapy is produced from clonal master iPSC lines, allowing for standardized, large-scale manufacturing.
- Other names
- CISH-knockout induced pluripotent stem cell-derived natural killer cellsCISH-deleted iNK cellsCISH-KO iPSC-derived NK cells
02
Targets
CISH (Cytokine-inducible SH2-containing protein)
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