CLL1 CAR T-CELL, METHOD OF ITS PRODUCTION AND ITS APPLICATION

Claims

1. A CLL1 CAR T cell comprising a chimeric antigen receptor, wherein said chimeric antigen receptor comprises a single-domain antibody, a hinge region, a transmembrane region and an intracellular signaling region, and the amino acid sequence of the single-domain antibody corresponds to positions 22-150 in SEQ ID NO:

1.

2. The CLL1 CAR T cell of claim 1, wherein the intracellular signaling region comprises a 4-1BB costimulatory domain and a CD3ζ activation domain, the amino acid sequence of 4-1BB corresponds to positions 220-266 in SEQ ID NO: 1, and the amino acid sequence of CD3ζ corresponds to positions 267-378 in SEQ ID NO:

1.

3. The CLL1 CAR T cell of claim 1 or 2, wherein the hinge region is a CD8a hinge region with an amino acid sequence corresponding to positions 151-195 in SEQ ID NO: 1, and the transmembrane region is a CD8a transmembrane region with an amino acid sequence corresponding to positions 196-219 in SEQ ID NO:

1.

4. The CLL1 CAR T cell according to any one of paragraphs 1-3, characterized in that the chimeric antigen receptor comprises any of the following: A1) a protein with the amino acid sequence presented in SEQ ID NO: 1 or positions 22-378 in SEQ ID NO: 1; A2) a protein obtained by substitution and / or deletion and / or addition of amino acid residues in the amino acid sequence presented in SEQ ID NO: 1 or positions 22-378 in SEQ ID NO: 1, which is characterized by more than 80% identity with the protein in A1) and the same function; A3) a fusion protein obtained by linking a tag or signal peptide to the N-terminus and / or C-terminus of A1) or A2), with the same function as A1).

5. A chimeric antigen receptor as defined in any one of paragraphs 1-4.

6. Biological material that is any of the following: B1) a nucleic acid molecule encoding a chimeric antigen receptor according to paragraph 5; B2) an expression cassette containing a nucleic acid molecule from B1); B3) a recombinant vector containing a nucleic acid molecule from B1), or a recombinant vector containing an expression cassette from B2); B4) a recombinant microorganism containing a nucleic acid molecule from B1), or a recombinant microorganism containing an expression cassette from B2), or a recombinant microorganism containing a recombinant vector from B3).

7. The biological material according to paragraph 6, characterized in that the nucleic acid molecule from B1) is any of the following: C1) a DNA molecule with a nucleotide sequence or coding sequence presented at positions 64-1134 in SEQ ID NO: 2; C2) a DNA molecule with more than 75% identity to the nucleotide sequence defined in C1) and with the same function; C3) a DNA molecule with a nucleotide sequence or coding sequence presented in SEQ ID NO: 2; C4) a DNA molecule with more than 75% identity to the nucleotide sequence from C3) and with the same function.

8. A pharmaceutical composition comprising a CLL1 CAR T cell according to any one of claims 1 to 4.

9. Any of the following uses of a CLL1 CAR T cell according to any one of claims 1-4, a chimeric antigen receptor according to claim 5, a biological material according to claim 6 or 7, or a pharmaceutical composition according to claim 8: D1) use in the preparation of a medicinal product for the prevention or treatment of tumors, or use in the prevention or treatment of tumors; D2) use in the preparation of a medicinal product for the prevention or treatment of diseases associated with a CLL1 target, or use in the prevention or treatment of diseases associated with a CLL1 target.

10. The use according to claim 9, characterized in that the diseases associated with the CLL1 target are CLL1-positive cancers.

11. The use according to claim 10, wherein the CLL1-positive cancer is acute myeloid leukemia, myelodysplastic syndrome or chronic myeloid leukemia.

12. A method for producing a CLL1 CAR T cell according to any one of claims 1 to 4, comprising transferring the nucleic acid molecule according to claim 6 or 7 into T cells for stable expression to produce a CLL1 CAR T cell.

13. A method for preventing or treating diseases associated with a CLL1 target, comprising administering a CLL1 CAR T cell according to any one of claims 1-4 or a pharmaceutical composition according to claim 8 to a subject suffering from diseases associated with a CLL1 target.

14. The method according to claim 13, characterized in that the diseases associated with the CLL1 target are CLL1-positive cancers.

15. The method according to claim 14, characterized in that the CLL1-positive cancer is acute myeloid leukemia, myelodysplastic syndrome, or chronic myeloid leukemia.