KAPPA/LAMBDA CHIMERIC ANTIGEN RECEPTORS

• US 20170049819A1
• Filed: 04/24/2015
• Published: 02/23/2017
• Est. Priority Date: 04/25/2014
• Status: Abandoned Application

• Current Assignee: bluebird bio, Inc.
• Original Assignee: bluebird bio, Inc.
• Inventors: Friedman, Kevin, Ryu, Byoung
• Application Number:
  US15/306,721
• Publication Number:
  US 20170049819A1
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 2239/38 characterised by the dose, timing or administration schedule
• CPC Class Codes: A61K 2239/48 Blood cells, e.g. leukemia or lymphoma
• CPC Class Codes: A61K 35/17 Lymphocytes; B-cells; T-cells; Natural killer cells; Interferon-activated or cytokine-activated lymphocytes when activated by a specific antigen A61K39/00
• CPC Class Codes: A61K 39/4611 T-cells, e.g. tumor infiltrating lymphocytes [TIL], lymphokine-activated killer cells [LAK] or regulatory T cells [Treg]
• CPC Class Codes: A61K 39/4631 Chimeric Antigen Receptors [CAR]
• CPC Class Codes: A61K 39/4644 Cancer antigens
• CPC Class Codes: C07K 14/70503 Immunoglobulin superfamily
• CPC Class Codes: C07K 14/7051 T-cell receptor (TcR)-CD3 complex
• CPC Class Codes: C07K 14/70514 CD4
• CPC Class Codes: C07K 14/70517 CD8
• CPC Class Codes: C07K 14/70521 CD28, CD152
• CPC Class Codes: C07K 14/70525 ICAM molecules, e.g. CD50, CD54, CD102
• CPC Class Codes: C07K 14/70532 B7 molecules, e.g. CD80, CD86
• CPC Class Codes: C07K 14/70575 NGF/TNF-superfamily, e.g. CD70, CD95L, CD153, CD154 NGF C07K14/48, TNF C07K14/525
• CPC Class Codes: C07K 14/70578 NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95 NGF-receptor C07K14/71, TNF-receptor C07K14/7151
• CPC Class Codes: C07K 14/70589 CD45
• CPC Class Codes: C07K 16/2803 against the immunoglobulin superfamily
• CPC Class Codes: C07K 16/4283 against an allotypic or isotypic determinant on Ig
• CPC Class Codes: C07K 2317/622 Single chain antibody (scFv)
• CPC Class Codes: C07K 2319/00 : Fusion polypeptide
• CPC Class Codes: C07K 2319/02 : containing a signal sequence
• CPC Class Codes: C07K 2319/03 : containing a transmembrane segment
• CPC Class Codes: C07K 2319/70 : containing domain for protein-protein interaction
• CPC Class Codes: C12N 2510/00 : Genetically modified cells
• CPC Class Codes: C12N 2740/16043 : viral genome or elements thereof as genetic vector
• CPC Class Codes: C12N 5/0636 : T lymphocytes

Abstract

The invention provides improved vector composition comprising chimeric antigen receptor for adoptive T cell therapies.

Claims

1. A chimeric antigen receptor (CAR) comprising:

a) an extracellular domain that binds one or more epitopes of a human kappa light chain polypeptide;

b) a transmembrane domain derived from a polypeptide selected from the group consisting of;

CD8a;

CD4, CD45, PD1, and CD152;

c) one or more intracellular co-stimulatory signaling domains selected from the group consisting of;

CD28, CD54 (ICAM), CD134 (OX40), CD137 (41BB), CD152 (CTLA4), CD273 (PD-L2), CD274 (PD-L1), and CD278 (ICOS); and

d) a CD3ζ

primary signaling domain.

2. The CAR of claim 1, wherein the extracellular domain comprises an antibody or antigen binding fragment that binds the human kappa light chain polypeptide.

3. The CAR of claim 2, wherein the antibody or antigen binding fragment that binds the kappa light chain polypeptide is selected from the group consisting of:

a Camel Ig, Ig NAR, Fab fragments, Fab′

fragments, F(ab)′

2 fragments, F(ab)′

3 fragments, Fv, single chain Fv antibody (“

scFv”

), bis-scFv, (scFv)2, minibody, diabody, triabody, tetrabody, disulfide stabilized Fv protein (“

dsFv”

), and single-domain antibody (sdAb, Nanobody).

4. The CAR of claim 3, wherein the antibody or antigen binding fragment that binds the kappa light chain polypeptide is an scFv.

5. The CAR of claim 2, wherein the antibody is a human antibody, a murine antibody, or a humanized antibody.

7. The CAR of claim 1, wherein the transmembrane domain is derived from CD8a.

8. The CAR of claim 1, wherein the one or more co-stimulatory signaling domains selected from the group consisting of:

CD28, CD134, and CD137.

13. The CAR of claim 1, further comprising a hinge region polypeptide.

17. The CAR of claim 1, further comprising a signal peptide.

19. A polynucleotide encoding a CAR of claim 1.

21. A vector comprising the polynucleotide of claim 19.

23. The vector of claim 21, wherein the vector is a viral vector.

25. The vector of claim 21, wherein the vector is a lentiviral vector.

39. An immune effector cell comprising the vector claim 21.

40. The immune effector cell of claim 39, wherein the immune effector cell is a T lymphocyte.

41. A composition comprising the immune effector cell of claim 39 and a physiologically acceptable excipient.

47. A method of treating a B cell malignancy in a subject in need thereof, comprising administering to the subject a therapeutically effect amount of the composition of claim 41.

48. The method of claim 47, wherein the B cell malignancy is multiple myeloma, chronic lymphocytic leukemia, or non-Hodgkin'"'"'s lymphoma.

49. The method of claim 48, wherein the MM is selected from the group consisting of:

overt multiple myeloma, smoldering multiple myeloma, plasma cell leukemia, non-secretory myeloma, IgD myeloma, osteosclerotic myeloma, solitary plasmacytoma of bone, and extramedullary plasmacytoma.

6. (canceled)

9-12. -12. (canceled)

14-16. -16. (canceled)

18. (canceled)

20. A polynucleotide encoding a CAR, wherein the polynucleotide sequence is set forth in SEQ ID NO:

1.

22. (canceled)

24. (canceled)

26-38. -38. (canceled)

42-46. -46. (canceled)

50. (canceled)