Second generation Seneca Valley virus oncolytic therapy: compositions and methods thereof
AssigneesSeneca Therapeutics, Inc., The Trustees of Columbia University in the City of New York
InventorsVincent R. Racaniello, Amy B. Rosenfeld, Paul L. Hallenbeck
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Abstract
Provided herein are compositions and methods of using Seneca Valley Virus (SVV) or a derivative thereof and an interferon type I (IFN-I) inhibiting agent comprising an mTOR inhibitor for treating a cancer in a subject. The disclosed methods particularly rely upon the expression level of an ANTXR1 and the expression level of IFN-I in the cancer from the subject. Also provided herein are methods for predicting the efficacy of an SVV treatment comprising IFN-I inhibiting agent.
Claims18
A method of treating a cancer in a subject in need thereof, the method comprising administering to the subject an interferon type I (IFN-I) inhibiting agent comprising an mTOR inhibitor and an effective amount of Seneca Valley Virus (SVV) or SVV derivative, wherein the cancer is non-permissive or minimally permissive to SVV infection and is characterized by:
- a. an expression level of anthrax toxin receptor 1 (ANTXR1) higher than an ANTXR1 reference value, and
- b. an expression level of IFN-I higher than an IFN-I reference value;
- and
- wherein the IFN-I inhibiting agent renders the cancer SVV-permissive.
A method of treating a cancer in a subject in need thereof, the method comprising administering to the subject an IFN-I inhibiting agent comprising an mTOR inhibitor and an effective amount of SVV or SVV derivative, wherein the cancer is non-permissive or minimally permissive to SVV infection and is characterized by an expression level of ANTXR1 higher than an ANTXR1 reference value, and wherein the IFN-I inhibiting agent reduces the expression level of IFN-I in the cancer thereby favoring replication of the SVV or the SVV derivative and reducing or eliminating the cancer.
A method of predicting the efficacy of a Seneca Valley Virus (SVV) treatment, or an SVV derivative treatment of a cancer non-permissive or minimally permissive to SVV infection in a subject in need thereof, the method comprising determining the expression level of ANTXR1 and the expression level of IFN-I in the cancer from the subject, wherein:
- a. an expression level of ANTXR1 higher than an ANTXR1 reference value, and
- b. an expression level of IFN-I higher than an IFN-I reference value are predictive that the treatment is effective, and wherein when the treatment is predicted to be effective, recommending treatment of the subject;
- and
- wherein the treatment comprises administering to the subject an IFN-I inhibiting agent comprising an mTOR inhibitor.
A pharmaceutical composition for treating a cancer non-permissive or minimally permissive to SVV infection in a subject in need thereof, the pharmaceutical composition comprising an IFN-I inhibiting agent comprising an mTOR inhibitor, an SVV or an SVV derivative, and a pharmaceutical acceptable carrier.
Dependencies are inferred from the claim text.