Anti-glypican-1-immunizing antigen receptor

Patent metadata

Field	Value
Publication number	US-11370845-B2
Application number	US-201615739580-A
Country	US
Kind code	B2
Filing date	Jun 24, 2016
Priority date	Jun 24, 2015
Publication date	Jun 28, 2022
Grant date	Jun 28, 2022

Abstract

The purpose of the present invention is to produce a chimeric antigen receptor (CAR) specific to glypican-1 (GPC-1) and to treat squamous cell carcinoma with genetically modified cells capable of expressing the CAR. The present invention provides: a chimeric antigen receptor for use in the treatment and/or prevention of squamous cell carcinoma, said chimeric antigen receptor comprising an extracellular domain capable of binding to GPC-1, a transmembrane domain and one or multiple intracellular domains, wherein at least one of the intracellular domains is an intracellular domain containing a primary cytosolic signaling sequence or an intracellular domain containing both a primary cytosolic signaling sequence and a secondary cytosolic signaling sequence; a genetically modified cell capable of expressing the chimeric antigen receptor; and a cell preparation containing the cell.

First claim

The invention claimed is:

1. A nucleic acid encoding a chimeric antigen receptor comprising an extracellular domain capable of binding to glypican-1 (GPC-1), a transmembrane domain and one or more intracellular domains, wherein at least one of the intracellular domains is an intracellular domain containing to comprise a primary cytosolic signaling sequence; wherein the extracellular domain capable of binding to GPC-1 comprises the heavy chain variable region (VH) and light chain variable region (VL) of anti-GPC-1 antibody and wherein the nucleotide sequence encoding the heavy chain variable region of anti-GPC-1 antibody comprises the nucleotide sequence listed as SEQ ID NO: 1 or a nucleotide sequence with at least 95% identity therewith and having the same function, and the nucleotide sequence encoding the light chain variable region comprises the nucleotide sequence listed as SEQ ID NO: 2 or a nucleotide sequence with at least 95% identity therewith and having the same function.

2. The nucleic acid of claim 1 , wherein the primary cytosolic signaling sequence comprises an immunoreceptor tyrosine-based activation motif (ITAM).

3. The nucleic acid of claim 2 , wherein the intracellular domain comprising the ITAM is derived from CD3ζ, FcRγ, FcRβ, CD3γ, CD3δ, CD3ε, CD5, CD22, CD79a, CD79b or CD66d.

4. The nucleic acid of claim 1 , wherein the chimeric antigen receptor further comprises one or more identical or differing intracellular domains comprising a secondary cytosolic signaling sequence.

5. The nucleic acid of claim 4 , wherein the intracellular domain comprising the secondary cytosolic signaling sequence is located at the N-terminal end of the intracellular domain comprising the primary cytosolic signaling sequence.

6. The nucleic acid of claim 4 , wherein the intracellular domain comprising the secondary cytosolic signaling sequence is derived from CD2, CD4, CDS, CD8a, CD8β, CD28, CD134, CD137, ICOS and/or CD154.

7. A chimeric antigen receptor encoded by the nucleic acid of claim 1 .

8. A vector comprising the nucleic acid of claim 1 .

9. Cells comprising the vector of claim 8 .

10. The cells of claim 9 , wherein the cells are T cells or a cell population comprising T cells.

11. A medical composition comprising the nucleic acid of claim 1 , and a medically acceptable excipient.

12. A nucleic acid encoding a chimeric antigen receptor comprising an extracellular domain capable of binding to glypican-1 (GPC-1), a transmembrane domain and one or more intracellular domains, wherein at least one of the intracellular domains is an intracellular domain containing to comprise a primary cytosolic signaling sequence for treatment of a solid tumor expressing GPC-1 and wherein the solid tumor is squamous cell carcinoma; wherein the extra cellular domain capable of binding to GPC-1 comprises the heavy chain variable region (VH) and light chain variable region (VL) of anti-GPC-1 antibody and wherein the nucleotide sequence encoding the heavy chain variable region of anti-GPC-1 antibody and wherein the anti-GPC-I antibody comprises the nucleotide sequence listed as SEQ ID NO: 1 or a nucleotide sequence with at least 95% identity therewith and having the same function, and the nucleotide sequence encoding the light chain variable region comprises the nucleotide sequence listed as SEQ ID NO: 2 or a nucleotide sequence with at least 95% identity therewith and having the same function.

Assignees

• Univ Keio
• Univ Nat Corp Kochi Univ

Inventors

• Yaguchi Tomonori
• Morii Kenji
• Kawakami Yutaka
• Kato Daiki
• Naka Tetsuji
• Serada Satoshi
• Fujimoto Minoru

Classifications

• A61K40/4261

  Proteoglycans, e.g. glypican, brevican or CSPG4 · CPC title

• A61K40/31

  Chimeric antigen receptors [CAR] · CPC title

• A61K40/11

  T-cells, e.g. tumour infiltrating lymphocytes [TIL] or regulatory T [Treg] cells; Lymphokine-activated killer [LAK] cells · CPC title

• A61K2239/50

  Colon · CPC title

• A61K2239/31

  characterized by the route of administration · CPC title