Combined chimeric antigen receptor targeting CD19 and CD20 and application thereof
The present invention provides a combined chimeric antigen receptor targeting CD19 and CD20 and application thereof. Specifically, the present invention provides a combined chimeric antigen receptor targeting CD19 and CD20, which comprises a scFv targeting CD19 and CD20, a hinge region, a transmembrane region, and an intracellular signaling domain. The present invention provides a nucleic acid molecule encoding the chimeric antigen receptor and a corresponding expression vector, a CAR-T cell, and applications thereof. The experimental results show that the chimeric antigen receptor provided by the present invention shows extremely high killing ability against tumor cells. The chimeric antigen receptor of the present invention targets CD19 and/or CD20 positive cells and can be used to treat CD19 and/or CD20 positive B-cell lymphoma, leukemia and other diseases.
1. A bispecific chimeric antigen receptor (CAR), comprising an amino acid sequence set forth in SEQ ID NO: 16, wherein the bispecific CAR comprises an anti-CD20 antigen-binding region and an anti-CD19 antigen-binding region.
2. An immune cell comprising the bispecific CAR of claim 1 .
3. The immune cell of claim 2 , wherein the immune cell is a T cell or a natural killer (NK) cell.
4. A pharmaceutical composition comprising the immune cell of claim 2 .
5. A nucleic acid encoding the bispecific CAR of claim 1 .
6. A vector comprising the nucleic acid of claim 5 .
7. A pharmaceutical composition comprising the vector of claim 6 .
8. An immune cell comprising the nucleic acid of claim 5 .
9. A pharmaceutical composition comprising the immune cell of claim 8 .
10. A nucleic acid, comprising a nucleic acid sequence set forth in SEQ ID NO: 18.
11. A vector comprising the nucleic acid of claim 10 .
12. A pharmaceutical composition comprising the vector of claim 11 .
13. An immune cell comprising the nucleic acid of claim 10 .
14. A pharmaceutical composition comprising the immune cell of claim 13 .
15. A method of treating a B-cell malignancy, the method comprising administering the immune cell of claim 3 to a subject in need thereof.
16. The method of claim 15 , wherein the immune cell is administered by infusion, injection, transfusion, implantation, and/or transplantation.
17. The method of claim 15 , wherein the immune cell is administered intravenously, subcutaneously, intramuscularly, intraperitoneally, or through spinal.
18. The method of claim 15 , wherein the immune cell is administered via intravenous infusion.
19. The method of claim 15 , wherein the immune cell is allogeneic or autologous.
20. The method of claim 15 , wherein the subject is a human.