Methods for the early diagnosis of ovarian cancer
AssigneeBoard of Trustees of the University of Arkansas
InventorsTimothy J. O'Brien, Martin J. Cannon, Alessandro Santin, John Beard, Kazushi Shigemasa
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Abstract
The present invention discloses the protease hepsin is specifically over-expressed in ovarian and other malignancies. A number of hepsin peptides can induce immune responses to hepsin, thereby demonstrating the potential of these peptides in monitoring and the development of immunotherapies for ovarian and other malignancies. There is also provided a hepsin protein variant that is useful as a marker for ovarian cancer cells, prostate cancer cells or kidney cancer cells.
Claims44
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.
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.
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.
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.
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.
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.
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.
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.
An immunogenic composition, comprising (i) a full length hepsin protein or a fragment of a hepsin protein and (ii) an appropriate adjuvant.
An oligonucleotide having a sequence complementary to SEQ ID No.188.
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.
An isolated DNA encoding a hepsin variant, said hepsin variant comprises the amino acid sequence of SEQ ID NO. 195 or a fragment thereof.
An isolated and purified hepsin variant protein, said hepsin variant comprises the amino acid sequence of SEQ ID NO. 195 or a fragment thereof.
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.
Dependencies are inferred from the claim text.