Multimodal trail molecules and uses in cellular therapies

Patent metadata

Field	Value
Publication number	US-2016333064-A1
Application number	US-201615225202-A
Country	US
Kind code	A1
Filing date	Aug 1, 2016
Priority date	Jan 31, 2011
Publication date	Nov 17, 2016
Grant date	—

Abstract

Described herein are novel compositions comprising multimodal TRAIL agents and cells engineered to express such multimodal TRAIL agents, including cells encapsulated in a scaffold or matrix, for use in the treatment of disorders such as cancer.

First claim

We claim:

1 . A cell comprising a nucleic acid sequence encoding a polypeptide comprising a soluble TRAIL fusion protein comprising a reporter module, a linker module, and a therapeutic TRAIL module comprising an extracellular domain of human TRAIL of SEQ ID NO: 1.

2 . The cell of claim 1 , wherein the cell is a stem cell.

3 . The cell of claim 2 , wherein the stem cell is an induced pluripotent stem cell.

4 . The cell of claim 1 , wherein the cell is a T cell.

5 . The cell of claim 1 , wherein the cell is encapsulated in a matrix or scaffold.

6 . The cell of claim 1 , wherein the therapeutic TRAIL module comprises amino acids 39-281 of SEQ ID NO: 1.

7 . The cell of claim 1 , wherein the therapeutic TRAIL module comprises amino acids 114-281 of SEQ ID NO: 1.

8 . The cell of claim 5 , wherein the matrix comprises a synthetic extracellular matrix.

9 . The cell of claim 5 , wherein the matrix is biodegradeable.

10 . The cell of claim 8 , wherein the synthetic extracellular matrix comprises a thiol-modified hyaluronic acid and a thiol-reactive cross-linker molecule.

11 . The cell of claim 10 , wherein the thiol-reactive cross-linker molecule is polyethylene glycol diacrylate.

12 . The cell of claim 1 , further comprising a nucleic acid sequence encoding HSV-TK.

13 . A cell comprising a heterologous nucleic acid sequence encoding a soluble TRAIL polypeptide comprising an extracellular domain of human TRAIL of SEQ ID NO: 1, wherein the cell is encapsulated in a matrix or scaffold.

14 . The cell of claim 13 , wherein the cell is a stem cell or a T cell.

15 . The cell of claim 14 , wherein the stem cell is an induced pluripotent stem cell.

16 . The cell of claim 13 , further comprising a nucleic acid sequence encoding HSV-TK.

17 . The cell of claim 13 , wherein the soluble TRAIL comprises amino acids 114-281 of SEQ ID NO: 1

18 . The cell of claim 13 , wherein the soluble TRAIL polypeptide comprises a fusion of human TRAIL polypeptide with an optical imaging reporter polypeptide.

19 . The cell of claim 13 , wherein the matrix comprises a synthetic extracellular matrix.

20 . The cell of claim 13 , wherein the matrix is biodegradable.

21 . The cell of claim 19 , wherein the synthetic extracellular matrix comprises a thiol-modified hyaluronic acid and a thiol-reactive cross-linker molecule.

22 . The cell of claim 21 , wherein the thiol-reactive cross-linker molecule is polyethylene glycol diacrylate.

Assignees

• Massachusetts Gen Hospital

Inventors

• Shah Khalid

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61L27/383

  Nerve cells, e.g. dendritic cells, Schwann cells · CPC title

• C07K2319/61

  containing an enzyme fusion for detection (lacZ, luciferase) · CPC title

• A61L27/58

  Materials at least partially resorbable by the body · CPC title

• C12Y207/01145

  Deoxynucleoside kinase (2.7.1.145) · CPC title