Engineering NK and T cells with metabolite-sensing receptors to target solid tumors - PubMed
4 hours ago
- #immunotherapy
- #solid tumors
- #metabolite-sensing receptors
- Engineering NK and T cells with metabolite-sensing receptors enhances their ability to target solid tumors.
- CRISPR activation screens identified GPR183, GPR84, GPR34, and GPR18 as top enhancers of NK cell infiltration and chemotaxis to breast and ovarian cancers.
- Expressing these receptors in NK and T cells drives migration to factors released by cancer cells and alters the NK cell transcriptome in a ligand-dependent manner.
- GPR183 expression in NK, CAR NK, and CAR T cells increased tumor infiltration and control.
- Mouse T cells expressing GPR183 showed increased tumor eradication in immunocompetent mice.
- Metabolite sensing can be rewired to guide spatially targeted cells, offering new therapeutic possibilities.