NUCLEIC ACID AND CORRESPONDING PROTEIN NAMED 158P1D7 USEFUL IN THE TREATMENT AND DETECTION OF BLADDER AND OTHER CANCERS
The invention described herein relates to novel nucleic acid sequences and their encoded proteins, referred to as 158P1D7 and variants thereof, and to diagnostic and therapeutic methods and compositions useful in the management of various cancers that express 158P1D7 and variants thereof.
1 . A method of generating a mammalian immune response directed to a protein, the method comprising:
exposing cells of the mammal's immune system to the protein, wherein the protein has an amino acid sequence selected from the group consisting of SEQ ID NO: 7, 9, or 11,
whereby an immune response is generated to said protein.
2 . The method of claim 1 , wherein the protein comprises at least one B cell epitope.
3 . The method of claim 2 , wherein exposing the immune system to the protein results in activation of a B cell which generates an antibody that specifically bind to the protein.
4 . A method for detecting the presence of a protein in a sample, comprising steps of:
contacting the sample with an antibody or fragment thereof that specifically binds to the protein has an amino acid sequence selected from the group consisting of SEQ ID NO: 7, 9, or 11, to form a complex; and,
determining the presence or amount of the complex in the sample.
5 . The method of claim 4 , wherein the tissue is selected from a tissue set forth in Table I.
6 . An antibody or fragment thereof that immunospecifically binds to an amino acid sequence selected from the group consisting of SEQ ID NO: 7, 9, or 11.
7 . The antibody or fragment thereof of claim 6 , which is monoclonal.
8 . The antibody or fragment thereof of claim 7 , wherein the monoclonal antibody is a recombinant protein.
9 . The antibody or fragment thereof of claim 8 , which is a single chain monoclonal antibody.
10 . The antibody or fragment thereof of claim 6 , wherein the fragment is an Fab, F(ab′) 2 , Fv or Sfv fragment.
11 . The antibody or fragment thereof of claim 6 , which is a human antibody.
12 . The antibody or fragment thereof of claim 6 , which is conjugated with a cytotoxic agent.
13 . The antibody or fragment thereof of claim 12 , wherein the cytotoxic agent is selected from the group consisting of radioactive isotopes, chemotherapeutic agents and toxins.
14 . The antibody or fragment thereof of claim 13 , wherein the radioactive isotope is selected from the group consisting of 211 At, 131 I, 125 I, 90 Y, 186 Re, 188 Re, 153 Sm, 212 Bi, 32 P and radioactive isotopes of Lu.
15 . The antibody or fragment thereof of claim 13 , wherein the chemotherapeutic agent is selected from the group consisting of taxol, actinomycin, mitomycin, etoposide, tenoposide, vincristine, vinblastine, colchicine, gelonin, and calicheamicin.
16 . The antibody or fragment thereof of claim 13 , wherein the toxin is selected from the group consisting of diphtheria toxin, enomycin, phenomycin, Pseudomonas exotoxin (PE) A, PE40, abrin, abrin A chain, mitogellin, modeccin A chain, and alpha-sarcin.
17 . The antibody or fragment thereof of claim 6 , wherein the antibody or fragment thereof further comprises a pharmaceutically acceptable carrier.
18 . A hybridoma that produces an antibody of claim 7 .
19 . A method of inhibiting viability, growth or reproduction status of cancer cells that express a protein, comprising:
administering to the cells an effective amount of an antibody or fragment thereof that immunospecifically binds to an amino acid sequence selected from the group consisting of SEQ ID NO: 7, 9, or 11, thereby inhibiting the viability, growth or reproduction status of said cells.