Adenovirus and immunomodulator combination therapy

Patent metadata

Field	Value
Publication number	US-11090344-B2
Application number	US-201716304359-A
Country	US
Kind code	B2
Filing date	May 30, 2017
Priority date	May 27, 2016
Publication date	Aug 17, 2021
Grant date	Aug 17, 2021

Abstract

Certain embodiments include the enhancement of effectiveness for an adenoviral cancer therapy.

First claim

The invention claimed is:

1. A method for treating and/or preventing a glioma in a mammal in need thereof, comprising administering to the mammal an effective amount of a combination comprising (a) a Delta24-RGD nucleic acid backbone, and a heterologous nucleic acid sequence encoding an OX40 agonist inserted in a nonessential region of the adenovirus genome, wherein the inserted heterologous nucleic acid sequence is under the control of a sequence permitting expression of the OX40 agonist and (b) one or more immune checkpoint inhibitors, wherein said one or more immune checkpoint inhibitor inhibits a checkpoint protein selected from the group consisting of PD-L1, programmed cell death protein 1 (PD-1), and PD-L2.

2. The replication competent oncolytic adenovirus of claim 1 , wherein the OX40 agonist is an OX40 ligand polypeptide.

3. The method of claim 1 , wherein the sequence permitting expression of the OX40 agonist is a CMV or RSV promoter.

4. The method of claim 1 , wherein the adenovirus genome further comprises a heterologous nucleic acid sequence encoding a tumor antigen.

5. The method of claim 1 , wherein the replication competent oncolytic adenovirus and the checkpoint inhibitor are administered simultaneously.

6. The method of claim 1 , wherein the replication competent oncolytic adenovirus and the checkpoint inhibitor are administered sequentially and wherein a first administration of oncolytic adenovirus occurs prior to a first administration of checkpoint inhibitor and preferably occurs within 30 days of a first administration of checkpoint inhibitor.

7. The method of claim 1 , wherein the checkpoint inhibitor is an antibody or fusion protein and is administered as one or more doses of 0.01-10 mg/kg, 0.1-10 mg/kg, 1-10 mg/kg, 2-8 mg/kg, 3-7 mg/kg, 4-5 mg/kg or at least 10 mg/kg.

8. The method of claim 1 , wherein the adenovirus is administered intratumorally, intravascularly, intratumorally and intravascularly or in a neuronal or mesenchymal stem cell carrier.

9. The method of claim 1 , wherein the adenovirus is administered once or multiple times at a dose of 10 8 -10 14 plaque forming units (pfu).

10. The method of claim 1 , wherein the mammal is a human.

11. The method of claim 10 , wherein the human has failed one or more treatments with an immune checkpoint inhibitor.

12. A method for treating and/or preventing cancer and/or treating and/or preventing a metastasis in a human subject in need thereof, comprising administering to the subject an effective amount of a replication competent oncolytic adenovirus according to claim 1 , wherein the immune checkpoint inhibitor and optionally the immune cell co-stimulatory receptor agonist is expressed in a cancer cell of the subject.

13. The method according to claim 1 wherein said wherein said one or more immune checkpoint inhibitor inhibits PD-1.

14. The method according to claim 13 , wherein said inhibitor of PD-1 is selected from the group consisting of Nivolumab, Pembrolizumab, and Pidilizumab.

Assignees

• Dnatrix Inc
• Univ Texas

Inventors

• Tufaro Frank
• Fueyo-Margareto Juan
• Gomez-Manzano Candelaria
• Conrad Charles
• Yung W K Alfred
• Jiang Hong

Classifications

• C12N2710/10343

  viral genome or elements thereof as genetic vector · CPC title

• A61K35/761 Primary

  Adenovirus · CPC title

• C07K16/28

  against receptors, cell surface antigens or cell surface determinants · CPC title

• C12N15/86

  Viral vectors · CPC title

• C12N2710/10332

  Use of virus as therapeutic agent, other than vaccine, e.g. as cytolytic agent · CPC title