Treatment and bioluminescent visualization using multimodal TRAIL molecules

Patent metadata

Field	Value
Publication number	US-9428565-B2
Application number	US-201213982343-A
Country	US
Kind code	B2
Filing date	Jan 31, 2012
Priority date	Jan 31, 2011
Publication date	Aug 30, 2016
Grant date	Aug 30, 2016

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

I claim:

1. A method of treatment and bioluminescent visualization for a subject having a malignant condition comprising administering a therapeutically effective amount of a pharmaceutical composition comprising a soluble TRAIL fusion protein comprising, in the following N-terminal to C-terminal order, a reporter module, a linker module of at least 8 amino acids, and a therapeutic TRAIL module, wherein said therapeutic TRAIL module comprises an extracellular domain of human TRAIL of SEQ ID NO: 1, and a pharmaceutically acceptable carrier.

2. The method of claim 1 , wherein the malignant condition is a glioblastoma.

3. The method of claim 1 , further comprising administering to the subject, one or more additional chemotherapeutic agents, biologics, drugs, or treatments as part of a combinatorial therapy.

4. The method of claim 3 , wherein the chemotherapeutic agent, biologic, drug, or treatment is selected from the group consisting of: radiation therapy, tumor resection surgery, gemcitabine, cisplastin, paclitaxel, carboplatin, bortezomib, AMG479, vorinostat, rituximab, temozolomide, rapamycin, ABT-737, and PI-103.

5. The method of claim 1 , wherein the pharmaceutical composition is administered at a surgical site.

6. The method of claim 5 , wherein the surgical site is a tumor resection site.

7. The method of claim 1 , wherein the linker domain comprises the amino acid sequence of SEQ ID NO: 4.

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

9. The method of claim 1 , wherein the therapeutic TRAIL module comprises amino acids 95-281 of SEQ ID NO: 1.

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

11. The method of claim 1 , wherein the therapeutic TRAIL module consists of amino acids 114-281 of SEQ ID NO: 1.

12. The method of claim 1 , wherein the soluble TRAIL fusion protein is encoded by a human stem cell comprising a nucleic acid sequence encoding the soluble TRAIL agent.

13. The method of claim 12 , wherein the human stem cell is encapsulated in a matrix or scaffold.

Assignees

• Shah Khalid
• Massachusetts Gen Hospital

Inventors

• Shah Khalid

Classifications

• C12N15/86

  Viral vectors · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• A61K47/36

  Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin · CPC title

• C07K2319/55

  containing a fusion with a toxin, e.g. diphteria toxin · CPC title

• A61K35/28

  Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells · CPC title