Methods, compositions and screens for therapeutics for the treatment of synovial sarcoma

Patent metadata

Field	Value
Publication number	US-10105420-B2
Application number	US-201615215284-A
Country	US
Kind code	B2
Filing date	Jul 20, 2016
Priority date	Mar 14, 2013
Publication date	Oct 23, 2018
Grant date	Oct 23, 2018

Abstract

Methods and compositions are provided for treating human synovial sarcoma (SS). Also provided are screens to identify therapeutics for the treatment of synovial sarcoma. These methods, compositions, and screens are based on the discovery that promoting the assembly of wild type BAF (also called mSWI/SNF) complexes in SS cells by increasing levels of wild type SS18 and/or decreasing levels of SS18-SSX fusion protein leads to the cessation of proliferation of malignant cells in synovial sarcoma.

First claim

That which is claimed is:

1. A method of promoting the assembly of wild-type BAF complexes in a cell, the method comprising:
contacting a cell comprising a mutant BAF complex with an effective amount of a wild-type BAF complex promoting agent to promote the assembly of wild-type BAF complexes in the cell, wherein the agent increases amounts in the cell of one or more of: wild type SS18 polypeptide, an active fragment of the wild type SS18 polypeptide, wild-type BAF47 polypeptide, and an active fragment of the wild-type BAF47 polypeptide.

2. The method according to claim 1 , wherein the mutant BAF complex comprises a SS18-SSX fusion polypeptide.

3. The method according to claim 2 , wherein the wild-type BAF complex promoting agent displaces the SS18-SSX fusion polypeptide from the mutant BAF complex.

4. The method according to claim 1 , wherein the wild-type BAF complex promoting agent increases the amount of wild type SS18 polypeptide in the cell.

5. The method according to claim 1 , wherein the cell is a human cell.

6. A method for treating human synovial sarcoma (SS) in an individual, the method comprising:
administering to an individual who has SS, an effective amount of a wild-type BAF complex promoting agent to promote the assembly of wild-type BAF complexes in SS cells comprising a mutant BAF complex and treat the individual for SS, wherein the agent increases amounts in SS cells of one or more of: wild type SS18 polypeptide, an active fragment of the wild type SS18 polypeptide, wild-type BAF47 polypeptide, and an active fragment of the wild-type BAF47 polypeptide.

7. The method according to claim 6 , wherein the mutant BAF complex comprises a SS18-SSX fusion polypeptide.

8. The method according to claim 7 , wherein the wild-type BAF complex promoting agent displaces the SS18-SSX fusion polypeptide from the mutant BAF complex.

9. The method according to claim 6 , wherein the wild-type BAF complex promoting agent increases the amount of wild type SS18 polypeptide in the cell.

10. The method according to claim 6 , further comprising administering chemotherapy to the individual.

11. The method according to claim 6 , further comprising administering radiotherapy to the individual.

Assignees

• Univ Leland Stanford Junior

Inventors

• Kadoch Cigall
• Crabtree Gerald R

Classifications

• G01N33/57557

  of other specific parts of the body, e.g. brain · CPC title

• A61K31/661

  Phosphorus acids or esters thereof not having P—C bonds, e.g. fosfosal, dichlorvos, malathion {or mevinphos} · CPC title

• A61K38/17

  from animals; from humans {(enzyme inhibitors A61K38/005)} · CPC title

• A61K45/06

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

• C12Q2600/156

  Polymorphic or mutational markers · CPC title