Immunologic effector cell of targeted CLD18A2, and preparation method and use thereof
Disclosed are a chimeric antigen receptor (CAR) targeting CLD18A2, and preparation method and use thereof. The extracellular binding region of the CAR comprises a protein specifically recognizing CLD18A2. The immune effector cell modified by the CAR can be used to treat tumors such as pancreatic cancer and stomach cancer.
1. A method for inducing cytotoxic effect against CLD18A2 positive cells, comprising contacting said CLD18A2 positive cells with immune effector cells having a chimeric antigen receptor (CAR) expressed, said CAR comprising an extracellular binding region, a transmembrane region and an intracellular signal region, wherein said extracellular binding region specifically recognizes CLD18A2.
2. The method of claim 1 , wherein said extracellular binding region comprises an antibody which specifically recognizes CLD18A2.
3. The method of claim 2 , wherein said antibody is a single-chain antibody or a single-domain antibody.
4. The method of claim 1 , wherein said extracellular binding region comprises an amino acid sequence having SEQ ID NO: 4 or SEQ ID NO: 6.
5. The method of claim 1 , wherein said transmembrane region has a sequence comprising the sequence of transmembrane region and hinge region of CD8 or CD28.
6. The method of claim 1 , wherein said intracellular signal region sequence is selected from the following: the intracellular signal region sequence of CD3ζ, FcεRIγ, CD27, CD28, CD137, CD134, or a combination thereof.
7. The method of claim 1 , wherein said immune effector cells comprise T lymphocytes, NK cells or NKT cells.
8. The method of claim 1 , wherein said CLD18A2 positive cells are tumor cells.
9. The method of claim 1 , wherein said immune effector cells are transduced by a nucleic acid having a sequence of SEQ ID NO: 3 or SEQ ID NO: 5.
10. The method of claim 9 , wherein said immune effector cells are transduced by an expression vector comprising said nucleic acid.
11. The method of claim 10 , wherein said expression vector is derived from lentivirus plasmid.