IP Library › Granted Patent US 12,234,274
Granted Patent B2
US 12,234,274 · App. 17/444,519 · Granted Feb 25, 2025

Use of the CD2 signaling domain in second-generation chimeric antigen receptors

Inventors: Carl H. June (Merion Station, PA); John Scholler (Narberth, PA); Avery D. Posey, Jr. (Philadelphia, PA)
Assignee: The Trustees of the University of Pennsylvania
C07K14/7051A61K39/4611A61K39/4631A61K39/464412A61K39/464468C07K14/705C07K14/70507C07K16/2803C07K16/30C12N15/85A61K2239/21A61K2239/48C07K2319/00C07K2319/02
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Quick Facts
Patent No.
US 12,234,274
App. No.
17/444,519
Granted
Feb 25, 2025
Kind
B2
Abstract

The present invention provides compositions and methods for treating cancer in a human. The invention includes relates to administering a genetically modified T cell expressing a CAR having an antigen binding domain, a transmembrane domain, a CD2 signaling domain, and a CD3 zeta signaling domain. The invention also includes incorporating CD2 into the CAR to alter the cytokine production of CAR-T cells in both negative and positive directions.

Claims (27)

1. An artificial nucleic acid sequence encoding a chimeric antigen receptor (CAR), wherein the artificial nucleic acid sequence comprises an in virto transcribed RNA and a 5′ cap and/or an internal ribosome entry site (IRES) sequence, and wherein the CAR comprises:

(a) an antigen binding domain having affinity for prostate specific membrane antigen (PSMA),

(b) a transmembrane domain,

(c) a costimulatory signaling region comprising a CD2 signaling domain, and

(d) a CD3 zeta signaling domain.

2. The nucleic acid sequence according to claim 1 , wherein the antigen binding domain is a Fab or a scFv.

3. The nucleic acid sequence according to claim 1 , wherein the antigen binding domain is a murine antigen binding domain.

4. The nucleic acid sequence according to claim 1 , wherein the antigen binding domain is a humanized antigen binding domain.

5. The nucleic acid sequence according to claim 1 , wherein the transmembrane domain is a CD8 transmembrane domain.

6. The nucleic acid sequence according to claim 1 , wherein the transmembrane domain is encoded by a nucleic acid sequence comprising nucleotides 924-995 of SEQ ID NO:1.

7. The nucleic acid sequence according to claim 1 , wherein the CAR further comprises a hinge domain.

8. The nucleic acid sequence according to claim 7 , wherein the hinge domain is a CD8 hinge domain.

9. The nucleic acid sequence according to claim 1 , wherein the CD2 signaling domain is encoded by a nucleic acid sequence comprising nucleotides 996-1346 of SEQ ID NO:1.

10. A composition comprising the nucleic acid sequence according to claim 1 .

11. A vector comprising the nucleic acid sequence according to claim 1 .

12. The vector according to claim 11 , wherein the nucleic acid sequence is operably linked to one or more expression control sequences.

13. The vector according to claim 11 , wherein the vector is an in vitro transcription (IVT) vector.

14. The vector according to claim 13 , wherein the IRES is a viral IRES, a chromosomal IRES, or an artificially designed IRES sequence.

15. A cell comprising the nucleic acid sequence according to claim 1 .

16. A cell comprising the vector according to claim 11 .

17. The cell according to claim 15 , wherein the cell is selected from the group consisting of bacterial cell, fungal cell, yeast cell, animal cell, and human cell.

18. The cell according to claim 17 , wherein the cell is an animal cell.

19. The cell according to claim 18 , wherein the animal cell is a human cell.

20. The cell according to claim 19 , wherein the human cell is an immune cell.

21. The cell according to claim 20 , wherein the immune cell is a T cell.

22. A method of generating a modified cell, the method comprising electroporting into a cell the nucleic acid sequence according to claim 1 .

23. The method according to claim 22 , wherein the cell is selected from the group consisting of bacterial cell, fungal cell, yeast cell, animal cell, and human cell.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 22, 2025
From: JUNE, CARL H.; POSEY, AVERY D., JR.; SCHOLLER, JOHN
To: THE TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA
Reel/Frame 069955/0873 →
CONFIRMATORY LICENSE Recorded Dec 13, 2023
From: UNIVERSITY OF PENNSYLVANIA
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 065968/0321 →
Continuity (5)
Continuation 16460221 · Jul 2, 2019
Division 15669562 · Aug 4, 2017
Division 14375999
Provisional Application 61601907 · Feb 22, 2012
Related Publication 20210371495A1 · Dec 2, 2021
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