CIRCULATING SURVIVIN-POSITIVE EXOSOMES

• US 20190331667A1
• Filed: 12/18/2017
• Published: 10/31/2019
• Est. Priority Date: 12/16/2016
• Status: Active Grant

• Current Assignee: Health Research Incorporated
• Original Assignee: Health Research Incorporated
• Inventors: FENSTERMAKER, Robert A., CIESIELSKI, Michael J.
• Granted Patent: US 11,467,152 B2
• Time in Patent Office: Days
• CPC Class Codes: A61K 39/0011 Cancer antigens
• CPC Class Codes: A61K 39/00115 Apoptosis related proteins, e.g. survivin or livin
• CPC Class Codes: A61K 9/127 Liposomes
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: G01N 2800/52 Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
• CPC Class Codes: G01N 2800/54 Determining the risk of relapse
• CPC Class Codes: G01N 2800/7028 Cancer
• CPC Class Codes: G01N 33/502 for testing non-proliferative effects
• CPC Class Codes: G01N 33/5076 involving cell organelles, e.g. Golgi complex, endoplasmic reticulum

Abstract

Provided is a method for evaluating the progression of glioma in an individual comprising monitoring the levels of circulating exosomes that are positive for survivin and a glial marker (such as glial fibrillary acidic protein). An increase in the level of such exosomes is indicative of poor prognosis. Levels of circulating exosomes that are positive for survivin and glial marker can also be used for evaluating the efficacy of a therapy for glioma in an individual, and modifying the therapy or introducing additional therapy if levels of such exosomes are found to be increasing.

Claims

1. A method for evaluating the efficacy of a therapy in an individual being treated for glioma comprising:

(i) determining a reference circulating level of exosomes that are positive for CD9, a glial marker, and survivin (CD9+/Glial marker+/SVN+ exosomes), (ii) at selected time during therapy, determining whether the level of circulating CD9+/Glial marker+/SVN+ exosomes in the individual is at or below the reference level, said determination indicating that the therapy is efficacious; and

(iii) continuing the therapy in the individual having a level of CD9+/Glial marker+/SVN+ exosomes at or below the reference level, or discontinuing or changing the therapy in the individual having a level of CD9+/Glial marker+/SVN+ exosomes above the reference level.

2. The method of claim 1, wherein the glial marker is glial fibrillary acidic protein.

3. The method of claim 1, wherein the circulating levels of CD9+/Glial marker+/SVN+ exosomes are determined in a biological fluid.

4. The method of claim 3, further comprising the step of obtaining an exosome rich fraction from the biological fluid prior to determining levels of CD9+/Glial marker+/SVN+ exosomes.

5. The method of claim 4, wherein the exosome rich fraction is at least 95% pure.

6. The method of claim 1, wherein the level of CD9+/Glial marker+/SVN+ exosomes in the biological fluid is determined by a combination of high resolution imaging and flow cytometry.

7. The method of claim 3, wherein the biological fluid is blood, plasma or serum.

8. The method of claim 1, wherein the therapy is one or more of surgery, radiation, and chemotherapy.

9. The method of claim 1, wherein the therapy is surgery followed by immunotherapy comprising administration of a composition comprising the peptide of SEQ ID NO:

1.

10. The method of claim 9, wherein step i) is carried out after surgical resection of the tumor but prior to administration of immunotherapy.

11. A method of treating an individual with a glioma comprising:

i) surgically removing the glioma;

ii) measuring a level of CD9+/Glial marker+/SVN+ exosomes;

iii) administering to the individual a composition comprising a peptide of SEQ ID NO;

1;

iv) at different times after administration of said composition, determining the level of circulating CD9+/Glial marker+/SVN+ exosomes in the individual; and

v) if the circulating levels of CD9+/Glial marker+/SVN+ exosomes are found to be above the reference level, then subjecting the individual to further treatment.

12. The method of claim 11, wherein the further treatment is surgery, radiation, chemotherapy, or immune therapy.

13. The method of claim 11, wherein the glial marker is glial fibrillary acidic protein.

14. A kit for evaluating the efficacy of a glioma treatment in an individual comprising:

detectably labeled antibodies for CD9+, detectably labeled antibody for a glial marker, detectably labeled antibody for survivin in suitable buffer, and optionally instructions for use of the antibodies for detection of circulating CD9+/Glial marker+/survivin+ exosomes in an individual.

15. The kit of claim 14, wherein the glial marker is glial fibrillary acid protein.