Method and compositions for enhancing immune response and for the production of in vitro mabs

• US 6,407,218 B1
• Filed: 11/10/1998
• Issued: 06/18/2002
• Est. Priority Date: 11/10/1997
• Status: Expired due to Term

• Current Assignee: CytImmune Sciences, Inc.
• Original Assignee: CytImmune Sciences, Inc.
• Inventors: Tamarkin, Lawrence, Paciotti, Giulio F.
• Primary Examiner(s): Saoud, Christine J.
• Assistant Examiner(s): HAMUD, FOZIA M
• Application Number:
  US09/189,748
• Time in Patent Office: 1,316 Days
• Field of Search: 530/389.1, 530/389.2, 530/391.1, 530/402, 530/387.1, 530/403, 530/808, 530/806, 436/547, 436/548, 424/85.1, 424/85.2, 424/130.1, 424/158.1, 514/2, 514/12
• US Class Current: 530/389.1
• CPC Class Codes: A61K 2039/55505 Inorganic adjuvants
• CPC Class Codes: A61K 2039/55516 Proteins; Peptides
• CPC Class Codes: A61K 2039/55522 Cytokines; Lymphokines; Interferons
• CPC Class Codes: A61K 47/64 Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent peptidic linkers A61K47/65
• CPC Class Codes: A61K 47/645 Polycationic or polyanionic oligopeptides, polypeptides or polyamino acids, e.g. polylysine, polyarginine, polyglutamic acid or peptide TAT
• CPC Class Codes: A61K 47/665 the pre-targeting system, clearing therapy or rescue therapy involving biotin-(strept) avidin systems
• CPC Class Codes: A61K 47/6923 the form being an inorganic particle, e.g. ceramic particles, silica particles, ferrite or synsorb
• CPC Class Codes: B82Y 5/00 Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
• CPC Class Codes: C07K 16/241 Tumor Necrosis Factors
• CPC Class Codes: C07K 2317/77 Internalization into the cell
• CPC Class Codes: Y10S 530/806 Antigenic peptides or proteins
• CPC Class Codes: Y10S 530/808 Materials and products related to genetic engineering or hybrid or fused cell technology, e.g. hybridoma, monoclonal products

Abstract

The methods and compositions of the present invention are directed to enhancing an immune response and increasing vaccine efficacy through the simultaneous or sequential targeting of specific immune system components. More particularly, specific immune components, such as macrophages, dendritic cells, B cells and T cells, are individually activated by component-specific immunostimulating agents. One such component-specific immunostimulating agent is an antigen-specific, species-specific monoclonal antibody. The invention is also directed to a method for the in vitro production of the antigen-specific, species-specific monoclonal antibodies which relies upon the in vitro conversion of blood-borne immune cells, such as macrophages and lymphocytes. Vaccine efficacy is enhanced by the administration of compositions containing component-specific immunostimulating agents and other elements, such as antigens or carrier particles, such as colloidal methods, such as gold.

Claims

1. An antigen-specific, human-specific monoclonal antibody comprised entirely of human protein, produced by a process consisting essentially of

a) stimulating immune cells from a human in vitro to activate the cells to produce a primary response to an antigen;

wherein the antigen is bond to colloidal metal and

b) immortalizing the activated immune cells; and

c) selecting a monoclonal antibody producing cell.

2. The composition of claim 1, wherein said antigen is selected from the group consisting of IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-11, IL-12, IL-13, lipid A, phospholipase A2, endotoxins, staphylococcal enterotoxin B and other toxins, Type I interferon, Type II interferon, TNF-α

, TGF-β

, lymphotoxin, migration inhibition factor, CSF, monocyte-macrophage CSF, granulocyte CSF, VEGF, angiogenin, heat shock proteins, carbohydrate moieties of blood groups, Rh factors, fibroblast growth factor, inflammatory and immune regulatory proteins, nucleotides, DNA, RNA, mRNA, sense, antisense, polynucleotides, cancer cell specific antigens, mutant p53, tyrosinase, autoimmune antigens, immunotherapy drugs, and angiogenic and anti-angiogenic drugs.

3. A method for the in vitro stimulation of immune cells to produce antigen-specific, species-specific monoclonal antibodies comprising

a) stimulating immune cells from a human or animal in vitro to activate the cells to produce a primary response to an antigen, wherein the antigen is bond to colloidal metal;

b) immortalizing the activated immune cells; and

c) selecting a monoclonal antibody producing cell.

4. The method of claim 3 wherein the stimulated immune cells produced in step (a) are stored and used at a later time.

5. The method of claim 3 wherein the species is mammalian.

6. The method of claim 5 wherein the species is human.

7. The method of claim 3 wherein said antigen is selected from the group consisting of IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-11, IL-12, IL-13, lipid A, phospholipase A2, endotoxins, staphylococcal enterotoxin B and other toxins, Type I interferon, Type II interferon, TNF-α

, TGF-β

, lymphotoxin, migration inhibition factor, CSF, monocyte-macrophage CSF, granulocyte CSF, VEGF, angiogenin, heat shock proteins, carbohydrate moieties of blood groups, Rh factors, fibroblast growth factor, inflammatory and immune regulatory proteins, nucleotides, DNA, RNA, mRNA, sense, antisense, polynucleotides, cancer cell specific antigens, mutant p53, tyrosinase, autoimmune antigens, immunotherapy drugs, and angiogenic and anti-angiogenic drugs.

8. A method for the in vitro production of antigen-specific, species-specific monoclonal antibodies comprising

a) incubating an antigen and antigen presenting cells in vitro to activate the antigen presenting cells, wherein the antigen is bond to colloidal metal;

b) adding B cells to the activated APCs to produce primary clones;

c) immortalizing the primary clones; and

d) selecting a monoclonal antibody producing cell.

9. The method of claim 8 wherein the stimulated immune cells produced in step (a) are stored and used at a later time.

10. The method of claim 8 wherein steps a) and b) are performed in a single step.

11. The method of claim 8 wherein the activation comprises at least one immunostimulating molecule.

12. The method of claim 8 wherein said antigen is selected from the group consisting of IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-11, IL-12, IL-13, lipid A, phospholipase A2, endotoxins, staphylococcal enterotoxin B and other toxins, Type I interferon, Type II interferon, TNF-α

, TGF-β

, lymphotoxin, migration inhibition factor, CSF, monocyte-macrophage CSF, granulocyte CSF, VEGF, angiogenin, heat shock proteins, carbohydrate moieties of blood groups, Rh factors, fibroblast growth factor, inflammatory and immune regulatory proteins, nucleotides, DNA, RNA, mRNA, sense, antisense, polynucleotides, cancer cell specific antigens, mutant p53, tyrosinase, autoimmune antigens, immunotherapy drugs, and angiogenic and anti-angiogenic drugs.