Microorganisms for imaging and/or treatment of tumors

• US 8,865,153 B2
• Filed: 05/10/2012
• Issued: 10/21/2014
• Est. Priority Date: 06/15/2007
• Status: Active Grant

• Current Assignee: Genelux Corporation, Sloan-Kettering Institute For Cancer Research (Memorial Sloan-Kettering Cancer Center)
• Original Assignee: Genelux Corporation
• Inventors: Szalay, Aladar A., Chen, Nanhai, Yu, Yong A., Zhang, Qian
• Primary Examiner(s): LI, BAO Q
• Application Number:
  US13/506,738
• Publication Number:
  US 20120244068A1
• Time in Patent Office: 894 Days
• US Class Current: 424/93.21
• 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: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 35/04 specific for metastasis
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: C07K 14/705 Receptors; Cell surface antigens; Cell surface determinants tumour specific antigens C07K14/4748
• CPC Class Codes: C12N 2710/24132 Use of virus as therapeutic agent, other than vaccine, e.g. as cytolytic agent
• CPC Class Codes: C12N 2710/24143 viral genome or elements thereof as genetic vector
• 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
• CPC Class Codes: G01N 33/574 for cancer
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

Modified viruses encoding transporter proteins and methods for preparing the modified viruses are provided. Vaccines that contain the viruses are provided. The viruses also can be used in diagnostic methods, such detection and imaging of tumors. The viruses also can be used in methods of treatment of diseases, such as proliferative and inflammatory disorders, including as anti-tumor agents.

Claims

1. A method of treatment, comprising administering a vaccinia virus to a subject to effect treatment, wherein:

the virus encodes a sodium-dependent transporter protein selected from among solute carrier 5 family and solute carrier 6 family transporter proteins, and also encodes a therapeutic agent; and

the virus is a Lister strain vaccinia virus.

2. The method of claim 1, wherein the subject is treated for a tumor, cancer or metastasis.

3. The method of claim 1, further comprising:

administering a substrate that is transported into a cell that expresses the transporter encoded by the virus, wherein;

the substrate is therapeutic or is conjugated to a therapeutic agent, whereby treatment is effected; and

the substrate is administered before or after or simultaneously with the virus.

4. The method of claim 3, wherein the subject has a tumor and the substrate or substrate conjugate is effective in treating a tumor.

5. The method of claim 1, wherein the virus is an LIVP strain virus.

6. The method of claim 5, wherein the virus is GLV-1h146 or GLV-1h150.

7. The method of claim 1, wherein nucleic acid encoding the transporter protein is inserted in the hemagglutinin (HA), thymidine kinase (TK) or F14.5 gene or locus.

8. The method of claim 7, wherein the nucleic acid encoding the therapeutic agent is inserted into a different gene or locus from the nucleic acid encoding the transporter protein and is inserted in the hemagglutinin (HA), thymidine kinase (TK) or F14.5 gene or locus.

9. The method of claim 1, wherein the therapeutic agent is an anti-cancer agent or anti-angiogenic agent or is selected from among a cytokine, a chemokine, an immuno-modulatory molecule, an antigen, an antibody or fragment thereof, an antisense RNA, a prodrug converting enzyme, an siRNA, an angiogenesis inhibitor, a toxin, an antitumor oligopeptide, a mitosis inhibitor protein, an antimitotic oligopeptide, an anti-cancer polypeptide antibiotic, and tissue factor.

10. The method of claim 9, wherein the therapeutic agent is an antibody or fragment thereof that is a single chain antibody (scFv).