Claims
- 1. A method of vaccinating an individual against hepsin, comprising the step of:
inoculating an individual with a hepsin peptide, wherein said hepsin peptide elicits an immune response in said individual, thereby vaccinating said individual against hepsin.
- 2. The method of claim 1, wherein said hepsin peptide is in peptide-loaded dendritic cells or is expressed from an expression vector.
- 3. The method of claim 1, wherein said individual has cancer, is suspected of having cancer or is at risk of getting cancer, wherein said cancer is selected from the group consisting of ovarian cancer, lung cancer, prostate cancer and colon cancer.
- 4. The method of claim 1, wherein the length of said hepsin peptide is from about 9-residue long to about 20-residue long.
- 5. The method of claim 4, wherein said peptide is selected from the group consisting of SEQ ID Nos. 28, 29, 30, 31, 88, 89, 108, 109, 128, 129, 148, 149, 150, 151, 152, 153, 154, 189, 190 and 191.
- 6. A method of producing immune-activated cells directed toward hepsin, comprising the steps of:
exposing immune cells to a hepsin protein or fragment thereof, wherein said exposure to said hepsin protein or fragment thereof activates said immune cells, thereby producing immune-activated cells directed toward hepsin.
- 7. The method of claim 6, wherein said immune cells are selected from the group consisting of B cells, T cells and dendritic cells.
- 8. The method of claim 6, wherein the length of said hepsin fragment is from about 9-residue long to about 20-residue long.
- 9. The method of claim 8, wherein said fragment is selected from the group consisting of SEQ ID Nos. 28, 29, 30, 31, 88, 89, 108, 109, 128, 129, 148, 149, 150, 151, 152, 153, 154, 189, 190 and 191.
- 10. The method of claim 7, wherein said dendritic cells are isolated from an individual prior to said exposure, wherein said activated dendritic cells are reintroduced into said individual subsequent to said exposure.
- 11. The method of claim 10, wherein said individual has cancer, is suspected of having cancer or is at risk of getting cancer, wherein said cancer is selected from the group consisting of ovarian cancer, lung cancer, prostate cancer and colon cancer.
- 12. A method of immunotherapy targeted toward hepsin in an individual, comprising the steps of:
a) isolating dendritic cells from said individual; b) expressing a hepsin protein or fragment thereof in said dendritic cells; and c) transferring said dendritic cells back to said individual, wherein said dendritic cells would activate hepsin-specific immune responses in said individual, thereby generating immunotherapy targeted toward hepsin in said individual.
- 13. The method of claim 12, wherein said individual has cancer, is suspected of having cancer or is at risk of getting cancer, wherein said cancer is selected from the group consisting of ovarian cancer, lung cancer, prostate cancer and colon cancer.
- 14. The method of claim 12, wherein said expression of hepsin in said dendritic cells is obtained by a mean selected from the group consisting of transfection, transduction and loading said dendritic cells with a hepsin protein or fragment thereof.
- 15. The method of claim 12, wherein the length of said hepsin fragment is from about 9-residue long to about 20-residue long.
- 16. The method of claim 15, wherein said fragment is selected from the group consisting of SEQ ID Nos. 28, 29, 30, 31, 88, 89, 108, 109, 128, 129, 148, 149, 150, 151, 152, 153, 154, 189, 190 and 191.
- 17. A method of immunotherapy targeted toward hepsin in an individual, comprising the steps of:
a) isolating dendritic cells from said individual; b) expressing a hepsin protein or fragment thereof in said dendritic cells; c) exposing immune cells comprising T cells isolated from said individual to said dendritic cells, wherein said dendritic cells would generate hepsin-specific T cells from said immune cells; and c) transferring said immune cells back to said individual, wherein said immune cells would activate hepsin-specific immune responses in said individual, thereby generating immunotherapy targeted toward hepsin in said individual.
- 18. The method of claim 17, wherein said individual has cancer, is suspected of having cancer or is at risk of getting cancer, wherein said cancer is selected from the group consisting of ovarian cancer, lung cancer, prostate cancer and colon cancer.
- 19. The method of claim 17, wherein said expression of hepsin in said dendritic cells is obtained by a mean selected from the group consisting of transfection, transduction and loading said dendritic cells with a hepsin protein or fragment thereof.
- 20. The method of claim 17, wherein the length of said hepsin fragment is from about 9-residue long to about 20-residue long.
- 21. The method of claim 20, wherein said fragment is selected from the group consisting of SEQ ID Nos. 28, 29, 30, 31, 88, 89, 108, 109, 128, 129, 148, 149, 150, 151, 152, 153, 154, 189, 190 and 191.
- 22. A method of monitoring the efficacy of vaccinating an individual with hepsin or hepsin peptide, said method comprises the steps of:
vaccinating said individual with said hepsin or hepsin peptide; isolating T cells from said individual; and measuring immune responses induced by said hepsin or hepsin peptide, wherein an increased level of immune responses compared to those exhibited by cells from normal individual indicates that said individual has been vaccinated by said hepsin or hepsin peptide.
- 23. The method of claim 22, wherein said immune response is selected from the group consisting of T cell proliferation induced by said hepsin or hepsin peptide, frequency of cytokine-secreting T cells specific to said hepsin or hepsin peptide and frequency of T cells expressing T cell receptor specific to said hepsin or hepsin peptide.
- 24. The method of claim 22, wherein said hepsin peptide is selected from the group consisting of SEQ ID Nos. 28, 29, 30, 31, 88, 89, 108, 109, 128, 129, 148, 149, 150, 151, 152, 153, 154, 189, 190 and 191.
- 25. A method of inhibiting expression of endogenous hepsin in a cell, comprising the step of:
introducing into said cell a vector comprising a sequence complementary to SEQ ID No.188, wherein expression of said vector in said cell produces hepsin antisense RNA that hybridizes to endogenous hepsin mRNA, thereby inhibiting expression of endogenous hepsin in said cell.
- 26. A method of inhibiting hepsin protein in a cell, comprising the step of:
introducing into said cell an antibody which is specific for a hepsin protein or a fragment thereof, wherein binding of said antibody to said hepsin protein or a fragment thereof inhibits hepsin protein in said cell.
- 27. The method of claim 26, wherein said hepsin protein fragment is selected from the group consisting of SEQ ID Nos. 28, 29, 30, 31, 88, 89, 108, 109, 128, 129, 148, 149, 150, 151, 152, 153, 154, 189, 190 and 191.
- 28. A method of targeted therapy to an individual, comprising the step of:
administering a compound to an individual, wherein said compound has a therapeutic moiety and a targeting moiety specific for hepsin.
- 29. The method of claim 28, wherein said targeting moiety is selected from the group consisting of an antibody specific for hepsin and a ligand or ligand binding domain that binds hepsin.
- 30. The method of claim 28, wherein said therapeutic moiety is selected from the group consisting of a radioisotope, a toxin, a chemotherapeutic agent, an immune stimulant and a cytotoxic agent.
- 31. The method of claim 28, wherein said individual suffers from a cancer selected from the group consisting of ovarian cancer, lung cancer, prostate cancer and colon cancer.
- 32. An immunogenic composition, comprising (i) a full length hepsin protein or a fragment of a hepsin protein and (ii) an appropriate adjuvant.
- 33. The immunogenic composition of claim 32, wherein the length of said hepsin fragment is from about 9-residue long to about 20-residue long.
- 34. The immunogenic composition of claim 33, wherein said fragment is selected from the group consisting of SEQ ID Nos. 28, 29, 30, 31, 88, 89, 108, 109, 128, 129, 148, 149, 150, 151, 152, 153, 154, 189, 190 and 191.
- 35. An oligonucleotide having a sequence complementary to SEQ ID No.188.
- 36. A composition comprising the oligonucleotide of claim 35 and a physiologically acceptable carrier.
- 37. A method of treating a neoplastic state in an individual in need of such treatment, comprising the step of:
administering to said individual an effective dose of the oligonucleotide of claim 35.
- 38. The method of claim 37, wherein said neoplastic state is selected from the group consisting of ovarian cancer, breast cancer, lung cancer, colon cancer and prostate cancer.
- 39. A method of screening for compounds that inhibit hepsin activity, comprising the steps of:
(a) contacting a sample comprising hepsin protein with a compound; and (b) assaying for hepsin protease activity, wherein a decrease in said hepsin protease activity in the presence of said compound relative to hepsin protease activity in the absence of said compound indicates said compound inhibits hepsin activity.
- 40. An isolated DNA encoding a hepsin variant, said hepsin variant comprises the amino acid sequence of SEQ ID NO. 195 or a fragment thereof.
- 41. An isolated and purified hepsin variant protein, said hepsin variant comprises the amino acid sequence of SEQ ID NO. 195 or a fragment thereof.
- 42. A method of detecting tumor cells in a sample, comprising the step of detecting the expression of a hepsin protein variant that comprises the amino acid sequence of SEQ ID NO. 195 or a fragment thereof, wherein the presence of said hepsin variant in said sample indicates that said sample contains tumor cells.
- 43. The method of claim 42, wherein said detection of hepsin variant expression or said or a fragment thereof is performed at DNA or protein level.
- 44. The method of claim 42, wherein said tumor cells are selected from the group consisting of ovarian cancer cells, prostate cancer cells and kidney cancer cells.
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This is a continuation-in-part application which claims the benefit of priority under 35 USC §120 of U.S. Ser. No. 10/135,795, filed Apr. 30, 2002, which is a continuation-in-part application which claims the benefit of priority under 35 USC §120 of U.S. Ser. No. 10/102,283, filed Mar. 20, 2002, which is a continuation-in-part application of U.S. Ser. No. 09/919,048, filed Jul. 30, 2001, which is a continuation-in-part application of U.S. Pat. No. 6,518,028, which is a divisional application of U.S. Pat. No. 6,268,165, which claims the benefit of priority under 35 USC §120 of U.S. Ser. No. 09/039,211, filed Mar. 14, 1998, which claims benefit of provisional patent application U.S. Ser. No. 60/041,404, filed Mar. 19, 1997, now abandoned.
Divisions (1)
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Number |
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09510738 |
Feb 2000 |
US |
Child |
09861966 |
May 2001 |
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Continuation in Parts (4)
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10135795 |
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10652993 |
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10102283 |
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10135795 |
Apr 2002 |
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09919048 |
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10102283 |
Mar 2002 |
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09861966 |
May 2001 |
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09919048 |
Jul 2001 |
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