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DKO CAR CB-NK cells
- Development stage
- Preclinical
- Lead developer
- Hospital Universitario 12 de Octubre
- Modality
- CAR-NK Cells → Other Engineered Cells → Adoptive Cell Transfer → Cell Therapies, CRISPR-Cas9 → CRISPR Systems → Programmable Nucleases → Gene Editing → Gene Therapies, Lymphokine-Activated Killer Cells → Native Immune Cells → Adoptive Cell Transfer → Cell Therapies
- Administration
- Intravenous
01
Overview
DKO CAR CB-NK cells are an experimental, allogeneic cell therapy consisting of cord blood-derived natural killer (NK) cells engineered with a chimeric antigen receptor (CAR) and modified via CRISPR/Cas9 gene editing. The cells express a CAR targeting B-cell maturation antigen (BCMA) with a 4-1BB costimulatory domain. The "DKO" (double knockout) designation refers to the simultaneous disruption of the KLRC1 gene (encoding the inhibitory receptor NKG2A) and the TGFBR2 gene (encoding the TGF-β receptor II). These genetic modifications are intended to enhance the cells' persistence and cytotoxic activity by making them resistant to immunosuppressive signals within the tumor microenvironment, such as the HLA-E/NKG2A axis and soluble TGF-β. The therapy is being developed by researchers at the Hospital 12 de Octubre and CIEMAT for the treatment of multiple myeloma.
- Other names
- double knockout CAR CB-NK cellsNKG2A/TGFBR2 knockout BCMA-CAR NK cellsDKO CAR NK cells
02
Targets
KLRC1 (Killer cell lectin-like receptor subfamily C member 1)BCMA (B-cell maturation antigen)
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