GENERATION OF ANTIBODIES TO TUMOR ANTIGENS AND GENERATION OF TUMOR SPECIFIC COMPLEMENT DEPENDENT CYTOTOXICITY BY ADMINISTRATION OF ONCOLYTIC VACCINIA VIRUS

• US 20150037355A1
• Filed: 01/04/2012
• Published: 02/05/2015
• Est. Priority Date: 01/04/2011
• Status: Active Grant

• Current Assignee: SillaJen, Inc.
• Original Assignee: Jennerex, Inc., SillaJen, Inc.
• Inventors: Kirn, David, Bell, John, Breitback, Caroline, Moon, Anne, Hwang, Tae-Ho, Lee, Yu Kyoung, Kim, Mi-kyung
• Granted Patent: US 9,919,047 B2
• Time in Patent Office: Days
• US Class Current: 424/174.1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 2039/507 Comprising a combination of two or more separate antibodies
• CPC Class Codes: A61K 2039/55522 Cytokines; Lymphokines; Interferons
• CPC Class Codes: A61K 35/26 Lymph; Lymph nodes; Thymus; Spleen; Splenocytes; Thymocytes
• CPC Class Codes: A61K 35/76 Viruses; Subviral particles; Bacteriophages
• CPC Class Codes: A61K 35/761 Adenovirus
• CPC Class Codes: A61K 35/763 Herpes virus
• CPC Class Codes: A61K 35/768 Oncolytic viruses not provided for in groups A61K35/761 - A61K35/766
• CPC Class Codes: A61K 39/0011 Cancer antigens
• CPC Class Codes: A61K 39/001102 Receptors, cell surface antigens or cell surface determinants
• CPC Class Codes: A61K 39/001106 Her-2/neu/ErbB2, Her-3/ErbB3 or Her 4/ErbB4
• CPC Class Codes: A61K 39/001164 GTPases, e.g. Ras or Rho
• CPC Class Codes: A61K 39/12 Viral antigens
• CPC Class Codes: A61K 39/125 Picornaviridae, e.g. calicivirus
• CPC Class Codes: A61K 39/145 Orthomyxoviridae, e.g. influenza virus
• CPC Class Codes: A61K 39/165 Mumps or measles virus
• CPC Class Codes: A61K 39/17 Newcastle disease virus
• CPC Class Codes: A61K 39/205 Rhabdoviridae, e.g. rabies virus
• CPC Class Codes: A61K 39/235 Adenoviridae
• CPC Class Codes: A61K 39/245 Herpetoviridae, e.g. herpes simplex virus
• CPC Class Codes: A61K 39/285 : Vaccinia virus or variola virus
• CPC Class Codes: A61K 39/395 : Antibodies agglutinins A61K38/36 ; as drug carriers A61K47/50; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
• CPC Class Codes: A61K 45/06 : Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 35/02 : specific for leukemia
• CPC Class Codes: A61P 37/04 : Immunostimulants
• CPC Class Codes: C07K 16/18 : against material from animals or humans
• CPC Class Codes: C07K 16/30 : from tumour cells
• CPC Class Codes: C07K 2317/14 : Specific host cells or culture conditions, e.g. components, pH or temperature
• CPC Class Codes: C07K 2317/734 : Complement-dependent cytotoxicity [CDC]
• CPC Class Codes: C12N 2710/10034 : Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
• CPC Class Codes: C12N 2710/16632 : Use of virus as therapeutic agent, other than vaccine, e.g. as cytolytic agent
• CPC Class Codes: C12N 2710/16634 : Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
• CPC Class Codes: C12N 2710/24034 : Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
• CPC Class Codes: C12N 2710/24132 : Use of virus as therapeutic agent, other than vaccine, e.g. as cytolytic agent
• CPC Class Codes: C12N 2720/12232 : Use of virus as therapeutic agent, other than vaccine, e.g. as cytolytic agent
• CPC Class Codes: C12N 2750/14034 : Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
• CPC Class Codes: C12N 2760/16034 : Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
• CPC Class Codes: C12N 2760/18134 : Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
• CPC Class Codes: C12N 2760/18434 : Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
• CPC Class Codes: C12N 2760/18734 : Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
• CPC Class Codes: C12N 2760/20034 : Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
• CPC Class Codes: C12N 2760/20232 : Use of virus as therapeutic agent, other than vaccine, e.g. as cytolytic agent
• CPC Class Codes: C12N 2770/32034 : Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
• CPC Class Codes: C12N 2770/32334 : Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
• CPC Class Codes: C12N 2770/36034 : Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
• 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

Abstract

The present invention relates to methods and compositions for use in inducing tumor-specific antibody mediated complement-dependent cytotoxic response in an animal having a tumor comprising administering to said animal a composition comprising a replication competent oncolytic virus wherein administration of the composition induces in the animal production of antibodies that mediate a CDC response specific to said tumor.

Claims

1. A method of inducing tumor-specific antibody mediated complement-dependent cytotoxic response in an animal having a tumor comprising administering to said animal a composition comprising a replication competent oncolytic virus wherein administration of said composition induces antibodies in said animal that mediate a CDC response specific to said tumor.

2. The method of claim 1 wherein administration of said oncolytic virus does not induce CDC response in an animal that does not have a tumor.

3. The method of claim 1 wherein said oncolytic virus is selected from the group consisting of a poxvirus, adenovirus, adeno-associated virus, herpes simplex virus, Newcastle disease virus, vesicular stomatitis virus, mumps virus, influenza virus, Parvovirus, measles virus, human hanta virus, myxoma virus, cytomegalovirus (CMV), lentivirus, Coxsackievirus, Echoviruses, Seneca Valley Virus and Sindbis virus.

4. The method of claim 1 wherein said oncolytic virus is an oncolytic poxvirus.

5. The method of claim 1 wherein said oncolytic virus is selected from the group consisting of JX-594, p53 expressing viruses, vesicular stomatitis virus (VSV), ONYX-15, Delta24, adenoviruses mutated in the VA1 region, vaccinia viruses mutated in the K3L or E3L region, Telomelysin, Telomelysin-GFP, parapoxvirus orf viruses mutated in the OV20.0L gene, Genelux virus, and herpes viruses mutated in the γ

(1)34.5 gene.

6. The method of claim 4 wherein said oncolytic poxvirus is vaccinia virus.

7. The method of claim 4 wherein said oncolytic virus is JX-594.

8. The method of claim 1 wherein said oncolytic virus comprises a transgene.

9. The method of claim 8 wherein said heterologous nucleic acid sequence encodes GM-CSF, cytosine deaminase, carboxyl esterase, NIS, stomatostatin receptor,

10. The method of claim 1 wherein said tumor is selected from the group consisting of astrocytoma, oligodendroglioma, meningioma, neurofibroma, glioblastoma, ependymoma, Schwannoma, neurofibrosarcoma, neuroblastoma, pituitary adenoma, medulloblastoma, head and neck cancer, melanoma, prostate carcinoma, renal cell carcinoma, pancreatic cancer, breast cancer, lung cancer, colon cancer, gastric cancer, bladder cancer, liver cancer, bone cancer, rectal cancer, ovarian cancer, sarcoma, gastric cancer, esophageal cancer, cervical cancer, fibrosarcoma, squamous cell carcinoma, neurectodermal, thyroid tumor, Hodgkin'"'"'s lymphoma, non-Hodgkin'"'"'s lymphoma, hepatoma, mesothelioma, epidermoid carcinoma, and tumorigenic diseases of the blood.

19. The method of claim 1 further comprising administering to said subject a further anti-cancer therapeutic agent.

11. A method of generating in vivo antibodies that mediate an anti-tumor CDC response comprising administering to a subject a composition comprising a replication competent oncolytic virus wherein administration of said composition induces production of antibodies that mediate a CDC response specific to said tumor.

12. The method of claim 11 further comprising harvesting blood from said subject after said administration and isolating CDC-response producing antibodies from said blood.

13. A composition comprising CDC-response producing antibodies isolated according to a method of claim 12.

14. The composition of claim 13 wherein said composition is serum collected from said subject.

15. A method of inhibiting the growth of or killing a cancer cell comprising contacting said cancer cell with a composition of claim 13.

16. The method of claim 15 wherein said contacting comprises contacting cancer cells in vitro with said composition.

17. The method of claim 15 wherein said contacting comprises infusing a subject having cancer with a composition comprising harvested antibodies, harvested B cells, antibodies produced by said harvested B cells or a combination thereof.

18. The method of claim 15 wherein said cancer cell is in vivo in a subject and said contacting comprising administering a medicament comprising said composition.

20. A method of treating a cancer subject comprising administering to said subject composition comprising a composition of claim 13.

21. The method of claim 20 wherein said composition is autologous to said patient and is isolated from the said cancer patient and reinfused into said cancer patient.

22. The method of claim 20 wherein said composition heterologous to said cancer patient is isolated from a cancer patient that is different from the cancer patient being treated with said composition.

23. The method of claim 20 wherein said subject is treated with a further anticancer therapeutic agent.

24. The method of claim 20 wherein said cancer subject has a solid tumor and said composition is administered intratumorally, intravenously, intraperitoneally or a combination thereof.

25. The method of claim 24 wherein said cancer subject has a solid tumor that is resected prior to, concurrently or subsequent to administering said composition of claim 12.

26. The method of claim 20 wherein said cancer subject has a solid tumor and said composition reduces the size of said tumor.

27. The method of claim 20 wherein said cancer subject has a solid tumor and said administration reduces metastatic spread of said solid tumor.

28. The method of claim 20 wherein said cancer is selected from the group consisting of astrocytoma, oligodendroglioma, meningioma, neurofibroma, glioblastoma, ependymoma, Schwannoma, neurofibrosarcoma, neuroblastoma, pituitary adenoma, medulloblastoma, head and neck cancer, melanoma, prostate carcinoma, renal cell carcinoma, pancreatic cancer, breast cancer, lung cancer, colon cancer, gastric cancer, bladder cancer, liver cancer, bone cancer, rectal cancer, ovarian cancer, sarcoma, gastric cancer, esophageal cancer, cervical cancer, fibrosarcoma, squamous cell carcinoma, neurectodermal, thyroid tumor, Hodgkin'"'"'s lymphoma, non-Hodgkin'"'"'s lymphoma, hepatoma, mesothelioma, epidermoid carcinoma, and tumorigenic diseases of the blood.

32. A method of identifying a tumor-specific antigen comprising

a) cloning a cDNA library prepared from a cancer cell into an expression vector;

b) performing a primary immunoscreen by contacting said expression vector with serum from a subject of claim 11 wherein said serum is isolated from said subject after administration of said oncolytic virus; and

c) isolating antigens from said cDNA library that are recognized by said serum.

33. The method of claim 11 further comprising administering to said subject a further anti-cancer therapeutic agent.

34. The method of claim 15 further comprising administering to said subject a further anti-cancer therapeutic agent.

29. A method of tailoring a cancer therapy for a subject having cancer comprising:

a) administering to said subject a composition comprising a replication competent oncolytic virus wherein administration of said composition induces in said subject production of antibodies that mediate a CDC response specific to said cancer in said subject;

b) isolating blood from said subject wherein said blood comprises harvested antibodies, harvested B cells against said cancer;

c) expanding or isolating said antibodies or producing antibodies from said B cells;

to produce an immunotherapy composition specific for said subject and

d) administering said subject with the immunotherapy composition of step (c).

30. The method of claim 29 wherein said immunotherapy composition is administered in immediately upon isolation of the antibodies.

31. The method of claim 29 wherein said immunotherapy composition is stored for further therapeutic treatment of said subject.