- Patent Number:
11965,014
- Appl. No:
17/638923
- Application Filed:
July 28, 2021
- نبذة مختصرة :
The present invention relates to a novel chimeric antigen receptor comprising a CD99 region which participates in immune synapse stabilization as a backbone of the chimeric antigen receptor, an immune cell comprising the same, and the uses thereof. CD99-based CAR-T cells are capable of forming very stable immune synapses with tumor cells compared to conventional backbone-based CAR-T cells and can exhibit improved tumor therapeutic efficiency, so they can be useful for immune cell therapy for the treatment of cancer.
- Inventors:
TICAROS CO., LTD. (Seoul, KR)
- Assignees:
TICAROS CO., LTD. (Seoul, KR)
- Claim:
1. A chimeric antigen receptor (CAR) comprising: (a) an antigen-binding domain; (b) a backbone comprising an extracellular spacer domain and a transmembrane domain; and (c) an intracellular signaling domain, wherein the transmembrane domain comprises a CD99 transmembrane domain, and wherein the chimeric antigen receptor comprises a CD99 intracellular juxtamembrane domain.
- Claim:
2. The chimeric antigen receptor according to claim 1 , wherein the CD99 transmembrane domain comprises an amino acid sequence represented by SEQ ID NO: 3.
- Claim:
3. The chimeric antigen receptor according to claim 1 , wherein the extracellular spacer domain comprises a CD99 extracellular domain.
- Claim:
4. The chimeric antigen receptor according to claim 3 , wherein the CD99 extracellular domain is represented by an amino acid sequence of SEQ ID NO: 5 or an amino acid sequence comprising contiguous 20 to 70 amino acid residues in the amino acid sequence of SEQ ID NO: 5.
- Claim:
5. The chimeric antigen receptor according to claim 3 , wherein the CD99 extracellular domain comprises an amino acid sequence represented by SEQ ID NO: 5, 7, 9, or 11.
- Claim:
6. The chimeric antigen receptor according to claim 1 , wherein the CD99 intracellular juxtamembrane domain comprises an amino add sequence represented by SEQ ID NO: 13.
- Claim:
7. The chimeric antigen receptor according to claim 1 , wherein the intracellular signaling domain comprises: an intracellular signaling domain selected from the group consisting of CD3 Zeta (ζ), CD3 gamma (γ), CD3 delta (δ), CD3 epsilon (ε), FcR gamma, FcR beta, CD5, CD22, CD79a, CD79b, and CD66d; and/or a co-stimulatory domain selected from the group consisting of CD2, CD7, CD27, CD28, CD30, CD40, 4-1 BB (CD137), OX40 (CD134), ICOS, LFA-1, GITR, MyD88, DAP1, PD-1, LIGHT, NKG2C, B7-H3, and a ligand specifically binding to CD83.
- Claim:
8. The chimeric antigen receptor according to claim 7 , wherein the CD3 Zeta (ζ) intracellular signaling domain comprises an amino acid sequence of SEQ ID NO: 17 or 19.
- Claim:
9. The chimeric antigen receptor according to claim 1 , wherein the antigen-binding domain comprises an antibody or antigen-binding fragment thereof that specifically binds to an antigen selected from the group consisting of: 4-18B, BCMA, BAFF, B7-H3, B7-H6, CA9, CTAG1B, CEA, cyclin, cyclin A2, cyclin B1, CCL-1, CCR4, CD3, CD4, CD19, CD20, CD22, CD23, CD24, CD30, CD33, CD38, CD40, CD44, CD44v6, CD44v7/8, CD52, CD58, CD62, CD79A, CD79B, CD80, CD123, CD133, CD138, CD171, CSPG4, CLDN18, CLDN6, CTLA-4, c-Met, DLL3, EGFR, tEGFR, EGFRvIII, EPG-2, EPG-40, ephrin B2, EPHA2, estrogen receptor, Fc receptor, FCRL5, FGF23, FBP, FOLR1, FOLR2, GD2, ganglioside GD3, gp100, GPC3, GPCR5D, GM-CSF, Her2/neu, Hera, Her4, erbB dimer, HMW-MAA, HBsAg, HLA-A1, HLA-A2, IL-22Ra, IL-13Ra2, ICOS, IGF-1 receptor, integrin αvβ6, interferon receptor, IFNγ, IL-2R, IL-4R, IL-5R, IL-6R, IL-17RA, IL-31IR, IL-36R, kdr, L1-CAM, CE7 epitope of L1-CAM, LRRC8A, Lewis Y, LAG3, MAGEA1, MAGEA3, MAGEA6, MAGEA10, MSLN, CMV, MUC1, NKG2D ligand, MART-I, NGF, NCAM, NRP-1, NRP-2, carcinoembryonic antigen, PD-L1, PRAME, progesterone receptor, prostate-specific antigen, PSCA, PSMA, RANKL, ROR1, SLAMF7, survivin, TPBG, TAG72, TRP1, TRP2, and Wilms' tumor 1 (WT1).
- Claim:
10. The chimeric antigen receptor according to claim 9 , wherein the antigen-binding fragment is a single-chain variable fragment (scFv) or nanobody of an antibody.
- Claim:
11. The chimeric antigen receptor according to claim 1 , further comprising a signal peptide at an N-terminus of the antigen-binding domain.
- Claim:
12. The chimeric antigen receptor according to claim 11 , wherein the signal peptide is a CD8α signal peptide comprising an amino acid sequence of SEQ ID NO: 25.
- Claim:
13. The chimeric antigen receptor according to claim 1 , wherein the chimeric antigen receptor comprises an amino acid sequence represented by SEQ ID NO: 27, 29, 31, or 33.
- Claim:
14. A nucleic acid encoding the chimeric antigen receptor according to claim 1 .
- Claim:
15. An expression vector comprising the nucleic acid according to claim 14 .
- Claim:
16. A virus comprising the expression vector according to claim 15 .
- Claim:
17. An immune cell expressing the chimeric antigen receptor according to claim 1 on a surface thereof.
- Claim:
18. The immune cell according to claim 17 , wherein the immune cell is a T cell, NK cell, NKT cell, or macrophage.
- Claim:
19. A composition for treating cancer comprising the immune cell according to claim 18 .
- Patent References Cited:
10766943 September 2020 Bachmann et al.
2017-530724 October 2017
WO-2018071583 April 2018
2019/136419 July 2019
- Other References:
Notice of Allowance issued in corresponding Korean Patent Application No. 10-2020-0094624 dated May 4, 2021. cited by applicant
Office Action issued in corresponding Korean Patent Application No. 10-2020-0094624 dated Sep. 24, 2020. cited by applicant
Gattinoni et al., “Adoptive immunotherapy for cancer: building on success,” Nature Reviews Immunology, 6 (5): 383-393 (2006). cited by applicant
Mardiana et al., “Supercharging adoptive T cell therapy to overcome solid tumor-induced immunosuppression,” Science Translational Medicine, 11: eaaw2293 (2019). cited by applicant
Van der Stegen et al., “The pharmacology of second-generation chimeric antigen receptors,” Nature Reviews Drug Discovery, 14 (7): 499-509 (2015). cited by applicant
Pata et al., “Association of CD99 short and long forms with MHC class I, MHC class II and tetraspanin CD81 and recruitment into immunological synapses,” CMC Research Notes, 4:293 (2011). cited by applicant
International Search Report issued in corresponding International Patent Application No. PCT/KR2021/009828 dated Nov. 9, 2021. cited by applicant
- Primary Examiner:
Skelding, Zachary S
- Attorney, Agent or Firm:
Morgan, Lewis & Bockius LLP
- الرقم المعرف:
edspgr.11965014
Processing Request
No Comments.