Enhanced immune response to an antigen by a composition of a recombinant virus expressing the antigen with a recombinant virus expressing an immunostimulatory molecule

• US 6,548,068 B1
• Filed: 01/07/2000
• Issued: 04/15/2003
• Est. Priority Date: 10/03/1994
• Status: Expired due to Term

• Current Assignee: United States Department Of Health And Human Services
• Original Assignee: United States Department Of Health And Human Services
• Inventors: Schlom, Jeffrey, Kantor, Judith, Hodge, James W.
• Primary Examiner(s): SALIMI, ALI REZA
• Application Number:
  US09/480,340
• Time in Patent Office: 1,194 Days
• Field of Search: 424/199.1, 424/232.1, 424/204.1, 435/320.1, 435/235.1, 435/325, 530/350, 530/387.1, 536/23.72
• US Class Current: 424/199.1
• CPC Class Codes: A61K 39/00 Medicinal preparations containing antigens or antibodies materials for immunoassay G01N33/53
• CPC Class Codes: A61K 39/46 Cellular immunotherapy
• CPC Class Codes: A61K 48/00 Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/12 Antivirals
• 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 14/705 Receptors; Cell surface antigens; Cell surface determinants tumour specific antigens C07K14/4748
• CPC Class Codes: C07K 14/70503 Immunoglobulin superfamily
• CPC Class Codes: C07K 14/70532 B7 molecules, e.g. CD80, CD86
• CPC Class Codes: C12N 2799/021 for the expression of a heterologous nucleic acid
• CPC Class Codes: C12N 2799/023 where the vector is derived from a poxvirus
• 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

The present invention is a composition of recombinant virus which has incorporated into its genome or portion thereof a gene encoding an antigen to a disease causing agent and a recombinant virus which has incorporated into its genome or portion thereof a gene encoding an immunostimulatory molecule(s) for the purpose of stimulating an immune response against the disease causing agent. Methods of treatment of diseases such as cancer and diseases caused by pathogenic microorganisms is provide using the composition.

Claims

1. A host cell infected with a recombinant vaccinia virus which has incorporated into a viral genome, at a region selected from the group consisting of Hind III F, F13L, HA, Hind III M, and TK, one or more genes or portion thereof encoding an antigen of a disease state and a gene or portion thereof encoding B7.2, or B7.1 and B7.2, resulting in coexpression of genes encoding the antigen of a disease state and genes encoding B7.2, or B7.1 and B7.2.

2. The host cell of claim 1 wherein the antigen is a tumor associated antigen.

3. The host cell of claim 2 wherein the tumor associated antigen is selected from the group consisting of oncofetal antigens, MART-1, Mage-1, Mage-3, gp100, tyrosinase, CEA, PSA, CA-125, erb-2, Muc-1, Muc-2, point mutated ras oncogenes, point mutated p53 oncogenes and TAG-72.

4. The host cell according to claim 1 wherein the recombinant virus further comprising one or more genes or portion thereof encoding an immunostimulatory molecule selected from the group consisting of IL-2, ICAM-1, LFA-3, CD72, GM-CSF, TNFα

, INFγ

, IL-12, IL-6 and combinations thereof.

5. The host cell according to any one of claims 1 to 4 wherein the host cell is an antigen presenting cell, a tumor cell, a cell infected with a pathogenic microorganism, or a genetically deficient cell.

6. The host cell of claim 5, wherein the antigen presenting cell is a dendritic cell or macrophage.

7. A pharmaceutical composition comprising the host cell according to claim 5 alone or in combination with an exogenous immunostimulatory molecule, chemotherapeutic drug, antibiotic, antiviral drug or anti-fungal drug and a pharmaceutically acceptable carrier.

8. A pharmaceutical composition comprising the host cell according to any one of claims 1 to 4 and a pharmaceutically acceptable carrier.

9. The pharmaceutical composition according to claim 8 further comprising an exogenous immunostimulatory molecule, chemotherapeutic drug, antibiotic, antiviral drug or anti-fungal drug.