Chimeric Receptors with 4-1BB Stimulatory Signaling Domain

Patent metadata

Field	Value
Publication number	US-2016009784-A1
Application number	US-201514872947-A
Country	US
Kind code	A1
Filing date	Oct 1, 2015
Priority date	Nov 4, 2004
Publication date	Jan 14, 2016
Grant date	—

Abstract

The present invention relates to a chimeric receptor capable of signaling both a primary and a co-stimulatory pathway, thus allowing activation of the co-stimulatory pathway without binding to the natural ligand. The cytoplasmic domain of the receptor contains a portion of the 4-1BB signaling domain. Embodiments of the invention relate to polynucleotides that encode the receptor, vectors and host cells encoding a chimeric receptor, particularly including T cells and natural killer (NK) cells and methods of use.

First claim

1 . (canceled)

2 . A polynucleotide encoding a chimeric receptor comprising: (a) an extracellular ligand-binding domain; (b) a transmembrane domain; and (c) a cytoplasmic domain comprising a 4-1BB signaling domain and a CD3C signaling domain.

3 . The polynucleotide of claim 2 , wherein said 4-1BB signaling domain is a human 4-1BB signaling domain.

4 . The polynucleotide of claim 2 , wherein said 4-1BB signaling domain comprises amino acid residues 214-255 of SEQ ID NO:2.

5 . The polynucleotide of claim 2 , wherein said transmembrane domain comprises a transmembrane domain of CD8α.

6 . The polynucleotide of claim 2 , wherein said chimeric receptor further comprises a hinge domain.

7 . A vector comprising a polynucleotide encoding a chimeric receptor comprising:
(a) an extracellular ligand-binding domain; (b) a transmembrane domain; and (c) a cytoplasmic domain comprising a 4-1BB signaling domain and a CD3ζ signaling domain.

8 . The vector of claim 7 , wherein said 4-1BB signaling domain is a human 4-1BB signaling domain.

9 . The vector of claim 7 , wherein said 4-1BB signaling domain comprises amino acid residues 214-255 of SEQ ID NO:2.

10 . The vector of claim 7 , wherein said vector is an expression vector, and wherein said polynucleotide is operably linked to at least one regulatory element in the appropriate orientation for expression.

11 . The vector of claim 10 , wherein said vector is a viral vector.

12 . The vector of claim 10 , wherein said vector is a retroviral vector.

13 . The vector of claim 7 , wherein said chimeric receptor further comprises a hinge domain.

14 . A host cell comprising a polynucleotide encoding a chimeric receptor comprising:
(a) an extracellular ligand-binding domain; (b) a transmembrane domain; and (c) a cytoplasmic domain comprising a 4-1BB signaling domain and a CD3ζ signaling domain.

15 . The host cell of claim 14 , wherein said 4-1BB signaling domain is a human 4-1BB signaling domain.

16 . The host cell of claim 14 , wherein said 4-1BB signaling domain comprises amino acid residues 214-255 of SEQ ID NO:2.

17 . The host cell of claim 14 , wherein said polynucleotide further comprises a promoter sequence.

18 . The host cell of claim 14 , wherein said chimeric receptor further comprises a hinge domain.

19 . The host cell of claim 14 , wherein said host cell is a T lymphocyte or an NK cell.

20 . The host cell of claim 14 , wherein said host cell is a T lymphocyte.

21 . The host cell of claim 14 , wherein said host cell is an NK cell.

Assignees

• St Jude Childrens Res Hospital

Inventors

• Campana Dario
• Imai Chihaya

Classifications

• A61K39/395

  Antibodies (agglutinins A61K38/36 {; as drug carriers A61K47/50}); Immunoglobulins; Immune serum, e.g. antilymphocytic serum · CPC title

• C07K16/2896

  against molecules with a "CD"-designation, not provided for elsewhere · CPC title

• C07K14/7051

  T-cell receptor (TcR)-CD3 complex · CPC title

• C07K14/70517

  CD8 · CPC title

• C12N2502/11

  blood or immune system cells · CPC title