Chimeric antigen receptor cells targeting ROBO1, preparation method and use thereof
AssigneeASCLEPIUS (Suzhou) TECHNOLOGY COMPANY GROUP CO., LTD.
InventorsHuashun Li, Baolei Wang, Kunkun Han
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Abstract
The present invention relates to chimeric antigen receptor cells targeting ROBO1, in particular, enhanced CAR-T cells and CAR-NK cells targeting ROBO1, and preparation and application thereof. The cells can stably expressing CAR elements, while secreting extracellular domain molecules expressing PD-1 protein or mutants thereof, and thus may block PD-11PD-L1 molecular interaction. It has been found through animal experiments that the cells have very good anti-tumor effects, and the above-mentioned cells can significantly reduce tumor recurrence and improve the survival rate compared with the conventional ROBO1-targeted CAR modified cells.
Claims8
A polynucleotide comprising a nucleotide encoding chimeric antigen receptor and a nucleotide encoding extracellular secretory protein, wherein the chimeric antigen receptor comprises an antigen-binding domain, a transmembrane domain and a costimulatory signaling region, and the antigen-binding domain is capable of specifically binding to FN3 domain of the tumor specific antigen ROBO1, and activating immune cells through the transmembrane domain and the costimulatory signaling region;
- the extracellular secretory protein is capable of preventing or inhibiting the binding of the wild type PD-1 protein to PD-L1 ligand;
- wherein, the extracellular secretory protein is the extracellular domain of PD-1 protein or the mutant of the extracellular domain, and the mutant of the extracellular domain is capable of binding PD-L1 with high affinity;
- wherein, the polynucleotide is a nucleotide encoding anti-ROBO1-FN3 scFv-CD8 transmembrane-4-1BB-CD3ζ-IRES-(the extracellular domain of PD-1 protein or mutant thereof), which has a sequence as shown in SEQ ID NO:
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Dependencies are inferred from the claim text.