Car expression vector and car-expressing T cells

Patent metadata

Field	Value
Publication number	US-10316102-B2
Application number	US-201515513870-A
Country	US
Kind code	B2
Filing date	Oct 6, 2015
Priority date	Oct 9, 2014
Publication date	Jun 11, 2019
Grant date	Jun 11, 2019

Abstract

A CAR expression vector comprises a nucleic acid encoding a chimeric antigen receptor (CAR) and a nucleic acid encoding a T cell immune function-enhancing factor, wherein the nucleic acid encoding an immune function-enhancing factor is a nucleic acid encoding interleukin-7 and a nucleic acid encoding CCL19, a nucleic acid encoding a dominant negative mutant of SHP-1, or a nucleic acid encoding a dominant negative mutant of SHP-2, or a CAR-expressing T cell introduced with the CAR expression vector are prepared.

First claim

The invention claimed is:

1. A CAR expression vector comprising a nucleic acid encoding a chimeric antigen receptor (CAR) and a nucleic acid encoding a T cell immune function-enhancing factor, wherein the nucleic acid encoding the T cell immune function-enhancing factor consists of a nucleic acid encoding interleukin-7 and a nucleic acid encoding CCL19.

2. The CAR expression vector according to claim 1 , wherein the nucleic acid encoding the CAR and the nucleic acid encoding the T cell immune function-enhancing factor are linked via a sequence encoding a self-cleaving peptide.

3. The CAR expression vector according to claim 1 , wherein the nucleic acid encoding interleukin-7 and the nucleic acid encoding CCL19 are linked via a sequence encoding a self-cleaving peptide.

4. The CAR expression vector according to claim 1 , wherein the nucleic acid encoding the CAR contains a nucleic acid encoding a polypeptide of a single chain antibody that recognizes FITC or CD20.

5. The CAR expression vector according to claim 1 , wherein the nucleic acid encoding the CAR contains a nucleic acid encoding a polypeptide of a CD8 transmembrane region.

6. The CAR expression vector according to claim 1 , wherein the nucleic acid encoding the CAR contains nucleic acids encoding polypeptides of a CD28 intracellular region, a 4-1BB intracellular region, and a CD3 intracellular region.

7. An isolated CAR-expressing T cell, or a culture comprising the isolated CAR-expressing T cell, said isolated T cell prepared by introducing the CAR expression vector according to claim 1 , and expressing the CAR, interleukin-7, and CCL19.

8. An isolated CAR-expressing T cell, or a culture comprising the isolated CAR-expressing T cell, said isolated T cell prepared by introducing the CAR expression vector according to claim 2 , and expressing the CAR, interleukin-7, and CCL19.

9. An isolated CAR-expressing T cell, or a culture comprising the isolated CAR-expressing T cell, said isolated T cell prepared by introducing the CAR expression vector according to claim 3 , and expressing the CAR, interleukin-7, and CCL19.

10. An isolated CAR-expressing T cell, or a culture comprising the isolated CAR-expressing T cell, said isolated T cell prepared by introducing the CAR expression vector according to claim 4 , and expressing the CAR, interleukin-7, and CCL19.

11. An isolated CAR-expressing T cell, or a culture comprising the isolated CAR-expressing T cell, said isolated T cell prepared by introducing a CAR expression vector that expresses a nucleic acid encoding a CAR and a nucleic acid encoding a first T cell immune function-enhancing factor, said first T cell immune function-enhancing factor consisting of interleukin-7, and a CAR expression vector that expresses a nucleic acid encoding a CAR and a nucleic acid encoding a second T cell immune function-enhancing factor, said second T cell immune function-enhancing factor consisting of CCL19; and expressing the CAR, interleukin-7, and CCL19.

12. An anticancer agent comprising the isolated CAR-expressing T cell according to claim 7 and a pharmaceutically acceptable additive.

13. An anticancer agent comprising the isolated CAR-expressing T cell according to claim 8 and a pharmaceutically acceptable additive.

14. An anticancer agent comprising the isolated CAR-expressing T cell according to claim 9 and a pharmaceutically acceptable additive.

15. An anticancer agent comprising the isolated CAR-expressing T cell according to claim 10 and a pharmaceutically acceptable additive.

16. An anticancer agent comprising the isolated CAR-expressing T cell according to claim 11 and a pharmaceutically acceptable additive.

17. The CAR expression vector of claim 1 wherein said interleukin-7 is human interleukin-7 and said CCL19 is human CCL19.

18. The isolated CAR-expressing T cell or cell culture of claim 7 , wherein said interleukin-7 is human interleukin-7 and said CCL19 is human CCL19.

19. The isolated CAR-expressing T cell or cell culture of claim 11 , wherein said interleukin-7 is human interleukin-7 and said CCL19 is human CCL19.

Assignees

• Univ Yamaguchi

Inventors

• Tamada Koji
• Sakoda Yukimi
• Adachi Keishi

Classifications

• C07K2319/33

  fusions for targeting to specific cell types, e.g. tissue specific targeting, targeting of a bacterial subspecies · CPC title

• C12N2510/00

  Genetically modified cells · CPC title

• C07K14/47 Primary

  from mammals · CPC title

• C07K16/2887 Primary

  against CD20 · CPC title

• C07K14/521

  Chemokines · CPC title