Biomarkers and combination therapies using oncolytic virus and immunomodulation

Patent metadata

Field	Value
Publication number	US-11065285-B2
Application number	US-202016917170-A
Country	US
Kind code	B2
Filing date	Jun 30, 2020
Priority date	Jan 25, 2012
Publication date	Jul 20, 2021
Grant date	Jul 20, 2021

Abstract

The invention disclosed herein describes biomarkers useful for prognosis, selection and monitoring of oncolytic virus therapy for patients with various types of cancer. In particular, the present invention provides identification of proteins whose expression patterns are strongly predictive of the outcome of oncolytic virus therapy in a patient with cancer. The present invention provides a method for identifying and selecting cancer patients who are likely to be non-responsive to onocolytic virus therapy. These patients can be co-administered an agent that stimulates a cell-mediated immune response in the patient with the oncolytic virus or can be administered a therapy other than oncolytic virus therapy.

First claim

The invention claimed is:

1. A method for treating a brain tumor in a patient having or suspected of having a primary or metastatic brain tumor comprising administering to said patient (a) an oncolytic virus selected from the group consisting of Delta-24 and Delta-24 RGD; and (b) a PD-1/PD-L1 receptor antagonist.

2. The method of claim 1 , wherein said PD-1/PD-L1 receptor antagonist is selected from the group consisting of MDX-1106, MK-3475, AMP-224, Pidilizumab, and MDX-1105.

3. The method of claim 1 , wherein the virus is administered intratumorally.

4. The method of claim 3 , wherein the virus is administered intratumorally by injection into multiple tumor sites.

5. The method of claim 1 , wherein the virus is administered intravascularly.

6. The method of claim 1 , wherein said brain tumor is a glioma.

7. The method of claim 6 , wherein the glioma is low-grade glioma.

8. The method of claim 6 , wherein the glioma is high-grade glioma.

9. The method of claim 1 , wherein the oncolytic virus is administered to the patient prior to the patient receiving a Th1 stimulating agent.

10. The method of claim 1 , wherein the oncolytic virus is administered to the patient after the patient receives a Th1 stimulating agent.

11. The method of claim 1 , where the brain tumor is primary brain tumor.

12. The method of claim 1 , where the brain tumor is metastatic brain tumor.

13. The method of claim 1 , wherein the virus is administered intravenously.

14. The method of claim 1 , wherein the virus is administered intraarterially.

Assignees

• Dnatrix Inc
• Univ Texas

Inventors

• Tufaro Frank
• Conrad Charles
• Fueyo-Margareto Juan
• Lang Jr Frederick
• Gomez-Manzano Candelaria
• Yung W K Alfred
• Heimberger Amy

Classifications

• G01N33/57585

  involving compounds identifiable in body fluids · CPC title

• G01N33/5758

  involving compounds serving as markers for tumours, cancers or neoplasias, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides or metabolites · CPC title

• A61P13/08

  of the prostate · CPC title

• A61K45/06

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

• A61K39/3955

  against proteinaceous materials, e.g. enzymes, hormones, lymphokines · CPC title