B CELL-BASED VACCINE LOADED WITH THE LIGAND OF NATURAL KILLER T CELL AND ANTIGEN

• US 20100028380A1
• Filed: 04/27/2006
• Published: 02/04/2010
• Est. Priority Date: 04/27/2006
• Status: Active Grant

• Current Assignee: Cellid Co., Ltd.
• Original Assignee: Seoul National University Industry Foundation (Seoul National University)
• Inventors: Kim, Byung-Seok, Kim, Yeon-Jeong, Ko, Sung-Youl, Ko, Hyun-Jeong, Kang, Chang-Yuil, Chung, Yeonseok
• Granted Patent: US 8,003,093 B2
• Time in Patent Office: Days
• US Class Current: 424/204.100
• CPC Class Codes: A61K 2039/80 Vaccine for a specifically defined cancer
• CPC Class Codes: A61K 2239/31 characterized by the route of administration
• CPC Class Codes: A61K 2239/38 characterised by the dose, timing or administration schedule
• CPC Class Codes: A61K 2239/55 Lung
• CPC Class Codes: A61K 2239/57 Skin; melanoma
• CPC Class Codes: A61K 39/4611 T-cells, e.g. tumor infiltrating lymphocytes [TIL], lymphokine-activated killer cells [LAK] or regulatory T cells [Treg]
• CPC Class Codes: A61K 39/4612 B-cells
• CPC Class Codes: A61K 39/4615 Dendritic cells
• CPC Class Codes: A61K 39/4622 Antigen presenting cells
• CPC Class Codes: A61K 39/4644 Cancer antigens
• CPC Class Codes: A61K 39/464402 Receptors, cell surface antigens or cell surface determinants
• CPC Class Codes: A61K 39/464406 Her-2/neu/ErbB2, Her-3/ErbB3 or Her 4/ ErbB4
• 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 relates to a B cell-based vaccine loaded with the ligand of natural killer T cell and antigen for the prevention and treatment of disease, more precisely, an immunotherapeutic and prophylactic vaccine mediated by B cells loaded with α-galactosylceramide, a kind of glycolipid which can stimulate natural killer T cells. A vaccine composition of the present invention can be effectively used as an antitumor immunotherapeutic agent. B cells therein, which are easily obtainable compared with dendritic cells, not only induce a similar level of cytotoxic T lymphocyte response to that of the conventional dendritic cell-based vaccine but also have a prophylactic and therapeutic effect on solid tumor and metastatic tumor.

Claims

1. An immunotherapeutic and prophylactic vaccine mediated by natural killer T cell ligand-loaded B cells, the ligand and antigen co-pulsed B cells or the ligand-loaded antigen-expressing B cells.

2. The immunotherapeutic and prophylactic vaccine according to claim 1, wherein the natural killer T cell ligand is selected from a group consisting of α

-galacturonosylceramide, α

-glucuronosylceramide, phosphatidylinositoltetramannoside, isoglobotrihexosylceramide, ganglioside GD3, phosphatidylcholine, β

-galactosylceramide, lipophosphoglycan, glycoinositol phospholipid, α

GalCer derivatives β

-anomeric galactosylceramide and α

-anomeric galactosylceramide, bacteria lipid antigen and α

GalCer variants.

3. The immunotherapeutic and prophylactic vaccine according to claim 1, wherein the antigen originated either from pathogens including pathogenic bacteria, virus and parasite or tumor antigen.

4. The immunotherapeutic and prophylactic vaccine according to claim 3, wherein the pathogenic bacteria derived antigen is selected from a group consisting of Bordetella pertussis antigen (pertussis toxin, filamentous hemagglutinin and pertactin), tetanus toxoid, diphtheria antigen (diphtheria toxoid), Helicobacter pylori antigen (capsula polysaccharides of serogrup A, B, C, Y and W-135), pneumococcal antigen (Streptococcus pnemoniae type 3 capsular polysaccharide), tuberculosis antigen, cholera antigen (cholera toxin B subunit), staphylococcal antigen (staphylococcal enterotoxin B), shigella antigen (shigella polysaccharides), Borrelia sp. antigen, Candida albicans antigen and Plasmodium antigen.

5. The immunotherapeutic and prophylactic vaccine according to claim 3, wherein the virus derived antigen is selected from a group consisting of influenza virus antigen (hemagglutinin and neuraminidase antigen), human papilloma virus (HPV) antigen (glycoprotein), vesicular stomatitis virus antigen (vesicular stomatitis virus glycoprotein), cytomegalovirus (CMV) antigen, hepatitis virus antigen (hepatitis A(HAV), B(HBV), C(HCV), D(HDV) and G(HGV) antigen) (core antigen and surface antigen), respiratory syncytial virus (RSV) antigen, herpes simplex virus (HSV) antigen, human immunodeficiency virus (HIV) antigen (GP-120, GP-160, p18, Tat, Gag, Pol and Env) and the combinations thereof.

6. The immunotherapeutic and prophylactic vaccine according to claim 3, wherein the tumor antigen is selected from a group consisting of HPV E6/E7, gp100, tyrosinase, TRP-1 (tyrosinase-related protein-1), TRP-2 (tyrosinase-related protein-2), MAGE, MUC-1, CEA (carcinoembryonic antigen), p53, alpha-fetoprotein and Her-2/neu.

7. The immunotherapeutic and prophylactic vaccine according to claim 1, wherein the antigen is characteristically in the form of peptide, lipopolysaccharide, polysaccharide, glycoprotein or polynucleotide.

8. The immunotherapeutic and prophylactic vaccine according to claim 1, wherein the antigen is expressed by transduction with a recombinant virus.

9. The immunotherapeutic and prophylactic vaccine according to claim 8, wherein the recombinant virus is selected from a group consisting of adenovirus, adeno-associated virus, retrovirus, vaccinia virus, poxvirus and Sindbis virus to introduce a gene encoding an antigen.

10. A natural killer T cell activator mediated by α

GalCer-loaded B cells.

11. A cytotoxic response inducer mediated by α

GalCer-loaded tumor antigen-expressing B cells.