Method for treating cancer with a Coxsackievirus B3 (CVB3) variant

• US 10,639,337 B2
• Filed: 09/29/2017
• Issued: 05/05/2020
• Est. Priority Date: 09/29/2017
• Status: Active Grant

• Current Assignee: Technische Universitã¤T Berlin (Tu)
• Original Assignee: Technische Universitã¤T Berlin (Tu)
• Inventors: Fechner, Henry, Hazini, Ahmet, Brueckner, Vanessa
• Primary Examiner(s): Gill, Rachel B
• Application Number:
  US15/720,850
• Publication Number:
  US 20190099460A1
• Time in Patent Office: 949 Days
• CPC Class Codes: A61K 31/7105 Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
• CPC Class Codes: A61K 35/76 Viruses; Subviral particles; Bacteriophages
• CPC Class Codes: A61K 35/768 Oncolytic viruses not provided for in groups A61K35/761 - A61K35/766
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C12N 2770/32321 Viruses as such, e.g. new isolates, mutants or their genomic sequences
• CPC Class Codes: C12N 2770/32332 Use of virus as therapeutic agent, other than vaccine, e.g. as cytolytic agent
• CPC Class Codes: C12N 2770/32371 Demonstrated in vivo effect
• CPC Class Codes: C12N 7/00 Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00

Abstract

The present invention relates to a method for treating cancer in a subject in need thereof, comprising administering to said subject a therapeutically effective amount of a Coxsackie B3 group virus or a modified form thereof, wherein the cells of the cancer express a heparan sulfate (HS) receptor on their surface and the virus binds to said HS receptor, enters and accumulates in the cancer cells, whereby at least some cancer cells undergo viral lysis.

Claims

1. A method for treating cancer in a subject in need thereof, comprising administering to said subject a therapeutically effective amount of a PD variant of the Coxsackie B3 group (CVB3) virus, wherein the PD variant is defined by an amino acid sequence comprising SEQ ID NO:

2, and wherein the cancer is selected from the group consisting of colorectal carcinoma, esophageal cancer, breast cancer, lung cancer, pancreatic cancer, prostate cancer, gastric cancer and liver cancer.

2. The method according to claim 1, wherein the PD variant of the CVB3 virus is defined by a nucleotide sequence comprising SEQ ID NO:

1.

3. The method according to claim 1, wherein the range of the therapeutically effective amount of the PD variant of the CVB3 virus is between about 5×

10⁵ to about 3×

10⁸ plaque forming units (PFU).

4. The method according to claim 1, wherein the cancer is colorectal carcinoma.

5. The method according to claim 1, wherein the cancer is in cells that express on their surface a receptor for the CVB3 PD variant, said receptor comprising a N- and/or a 6-O-sulfated heparan.

6. A pharmacological composition, comprising:

i) a therapeutically effective amount of a PD variant of the Coxsackie B3 group (CVB3) virus, wherein the PD variant is defined by an amino acid sequence comprising SEQ ID NO;

2; and

ii) at least one pharmaceutically acceptable excipient, diluent or carrier.

7. The composition according to claim 6, wherein the PD variant of the CVB3 virus is defined by a nucleotide sequence comprising SEQ ID NO:

1.

8. The composition according to claim 6, wherein the pharmacological composition is used for treating cancer where the cancer cells express on their surface a receptor for the CVB3 PD variant, said receptor comprising a N- and/or a 6-O-sulfated heparan.

13. The composition according to claim 6, wherein the range of the therapeutically effective amount of the PD variant of the CVB3 virus is between about 5×

10⁵ to about 3×

10⁸ plaque forming units (PFU).

9. A method for treating cancer in a subject in need thereof, said method comprising the steps of:

(i) confirming expression of heparin sulfate (HS) on the surface of a target population of cancer cells in a subject; and

(ii) administering to said subject a therapeutically effective amount of a PD variant of the Coxsackie B3 group (CVB3) virus to infect said target population of cancer cells via binding to at least said HS, causing infected cancer cells to undergo viral lysis, wherein the CVB3 PD variant is defined by an amino acid sequence comprising SEQ ID NO;

2.

10. The method according to claim 9, wherein the CVB3 PD variant is further defined by a nucleotide sequence comprising SEQ ID NO:

1.

11. The method according to claim 9, wherein the cancer is selected from the group consisting of colorectal carcinoma, esophageal cancer, breast cancer, lung cancer, pancreatic cancer, prostate cancer, gastric cancer and liver cancer.

12. The method according to claim 9, wherein step (i) comprises using an antibody against a heparan sulfate or a sulfotransferase.