Chimeric antigen receptors, compositions, and methods

• US 10,640,570 B2
• Filed: 01/28/2016
• Issued: 05/05/2020
• Est. Priority Date: 01/29/2015
• Status: Active Grant

• Current Assignee: Regents of The University of Minnesota (University of Minnesota)
• Original Assignee: Regents of The University of Minnesota (University of Minnesota)
• Inventors: Kaufman, Dan Samuel, Lampi Hermanson, David Lee, Moriarity, Branden Scott
• Primary Examiner(s): Leavitt, Maria G
• Application Number:
  US15/546,177
• Publication Number:
  US 20180002438A1
• Time in Patent Office: 1,559 Days
• Field of Search: None
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 2239/31 characterized by the route of administration
• CPC Class Codes: A61K 2239/38 characterised by the dose, timing or administration schedule
• 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 39/4613 Natural-killer cells [NK or NK-T]
• CPC Class Codes: A61K 39/4631 Chimeric Antigen Receptors [CAR]
• CPC Class Codes: A61K 39/464402 Receptors, cell surface antigens or cell surface determinants
• CPC Class Codes: A61K 39/464468 Mesothelin [MSLN]
• CPC Class Codes: A61P 1/18 for pancreatic disorders, e.g. pancreatic enzymes
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 37/04 Immunostimulants
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 14/4747 Apoptosis related proteins
• CPC Class Codes: C07K 14/54 Interleukins [IL]
• CPC Class Codes: C07K 14/705 Receptors; Cell surface antigens; Cell surface determinants tumour specific antigens C07K14/4748
• CPC Class Codes: C07K 14/7051 T-cell receptor (TcR)-CD3 complex
• 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 14/70596 Molecules with a "CD"-designation not provided for elsewhere
• CPC Class Codes: C07K 16/30 : from tumour cells
• CPC Class Codes: C07K 2319/02 : containing a signal sequence
• CPC Class Codes: C07K 2319/03 : containing a transmembrane segment
• CPC Class Codes: C07K 2319/33 : fusions for targeting to specific cell types, e.g. tissue specific targeting, targeting of a bacterial subspecies
• CPC Class Codes: C07K 2319/40 : containing a tag for immunodetection, or an epitope for immunisation
• CPC Class Codes: C07K 2319/70 : containing domain for protein-protein interaction
• CPC Class Codes: C07K 2319/74 : containing a fusion for binding to a cell surface receptor
• CPC Class Codes: C12N 5/0646 : Natural killers cells [NK], NKT cells

Abstract

This disclosure describes chimeric antigen receptors for expression in a Natural Killer (NK) cell, pharmaceutical compositions that include NK cells (and/or iPSCs) modified to express a chimeric antigen receptor, and methods involving such chimeric antigen receptors. Generally, the chimeric antigen receptor includes an ectodomain that includes an antigen recognition region, a transmembrane domain linked to the ectodomain, and an endodomain linked to the transmembrane domain. The endodomain can include a signaling peptide that activates an NK cell.

Claims

1. A chimeric antigen receptor molecule comprising, in an N-terminus to C-terminus orientation:

an ectodomain comprising an antigen recognition region;

a hinge;

a transmembrane domain comprising a transmembrane region of NKG2D (cluster of differentiation 314 or CD314) in reverse orientation as compared to native NKG2D that natively has an extracellular C-terminus; and

an endodomain comprising a functional signaling domain that activates a Natural Killer (NK) cell, wherein said functional signaling domain is selected from the group consisting of;

(a) a 2B4 (cluster of differentiation 244 or CD244) intracellular domain (ICD) and a CD3 zeta (CD3ζ

) signaling domain;

(b) a 41BB (cluster of differentiation 137 or CD137) ICD and a CD3ζ

signaling domain;

(c) a DAP12 (DNAX activation protein of 12 kDa) ICD and a CD3ζ

signaling domain;

(d) a 2B4 ICD, a 41BB ICD and a CD3ζ

signaling domain;

(e) a IL21R ICD and a CD3ζ

signaling domain; and

(f) a 41BB ICD, a 2B4 ICD and a CD3ζ

signaling domain.

2. The chimeric antigen receptor of claim 1 wherein the antigen recognition domain specifically binds an antigen associated with a disease.

3. The chimeric antigen receptor of claim 1 wherein the antigen recognition domain specifically binds a tumor antigen.

4. The chimeric antigen receptor of claim 1 wherein the ectodomain further comprises a signal peptide or leader sequence.

5. The chimeric antigen receptor of claim 1, wherein said hinge is a CD8α

hinge.

6. A pharmaceutical composition comprising an NK cell that expresses the chimeric antigen receptor of claim 5.

7. The pharmaceutical composition of claim 6, wherein the NK cell is derived from an iPSC.