Mammalian SIMP protein, gene sequence and uses thereof in cancer therapy
OwnerClaude Perreault, Kevin McBrideinventors
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Abstract
This invention provides SIMP nucleic acid and sequences. Also provided are methods for using SIMP nucleic acids, proteins, fragments, antibodies, probes, and cells, to characterize SIMP, modulate SIMP cellular levels, modulate immune responses and diagnose and treat cancers.
Claims83
An isolated or purified human nucleic acid molecule encoding a human protein that is expressed ubiquitously in human cells, wherein said protein has the potential of generating a plurality of protein fragments binding with high affinity to a human HLA molecule.
An isolated or purified human nucleic acid molecule comprising a polynucleotide having a nucleotide sequence selected from the group consisting of:
- a) a nucleotide sequence having greater than 63% nucleotide sequence identity with SEQ ID NO:
- 7;
- b) a nucleotide sequence having greater than 63% nucleotide sequence identity with a nucleic acid encoding an amino acid sequence of SEQ ID NO:8;
- c) a nucleotide sequence having at least 91% nucleotide sequence identity with SEQ ID NO:
- 1;
- d) a nucleotide sequence having at least 91% nucleotide sequence identity with a nucleic acid encoding an amino acid sequence of SEQ ID NO:
- 2;
- and
- e) a nucleotide sequence complementary to any of the nucleotide sequences in (a), (b), (c) or (d).
An isolated or purified human nucleic acid molecule comprising a polynucleotide having the SEQ ID NO:
- 1, or degenerate variants thereof, and encoding a human SIMP polypeptide.
An isolated or purified human protein that is expressed ubiquitously in human cells, wherein said protein has the potential of generating a plurality of protein fragments binding with high affinity to a human HLA molecule.
An isolated or purified polypeptide comprising an amino acid sequence selected from the group consisting of:
- a) an amino acid sequence having greater than 71% amino acid sequence identity to SEQ ID NO:
- 8;
- b) an amino acid sequence having greater than 71% amino acid sequence identity to an amino acid sequence encoded by an open reading frame having SEQ ID NO:
- 7;
- c) an amino acid sequence having greater than 82% amino acid sequence homology to SEQ ID NO:
- 8;
- d) an amino acid sequence having greater than 82% amino acid sequence homology to an amino acid sequence encoded by an open reading frame having SEQ ID NO:
- 7;
- e) an amino acid sequence having greater than 97% amino acid sequence identity to SEQ ID NO:
- 2;
- f) an amino acid sequence having greater than 97% amino acid sequence identity to an amino acid sequence encoded by an open reading frame having SEQ ID NO:
- 1;
- g) an amino acid sequence having greater than 97% amino acid sequence homology to SEQ ID NO:
- 2;
- and
- h) an amino acid sequence having greater than 97% amino acid sequence homology to an amino acid sequence encoded by an open reading frame having SEQ ID NO:
- 1
A substantially pure human SIMP polypeptide, or fragment thereof.
An isolated or purified human protein that is a paralog of a human protein having SEQ ID NO:12.
An isolated or purified polypeptide fragment, said fragment comprising at least eight sequential amino acids of SEQ ID NO:
- 2.
An isolated or purified polypeptide having a high binding affinity for a human HLA molecule, said polypeptide comprising at least eight amino acids having a sequence identity that is greater than 97% to a portion of a human protein that is expressed ubiquitously in human cells.
An antisense nucleic acid which hybridizes under high stringency condition to SEQ ID NO:
- 1 or to a complementary sequence thereof.
An antisense nucleic acid that reduces human SIMP′ cellular levels of expression.
A pharmaceutical composition comprising a human SIMP antisense nucleic acid.
A method for eliminating tumoral cells in a mammal, comprising the step of injecting, into said mammal's circulatory system, T-lymphocytes that recognize a immune complex that is present at the surface of said tumoral cells, said immune complex consisting of a SIMP protein fragment or a ITM1 protein fragment bound to an MHC molecule.
A method for increasing cell proliferation in a mammal, comprising the step of:
- i) contacting said cell with a SIMP polypeptide;
- and/or ii) increasing cellular expression levels of a SIMP polypeptide.
A method for modulating tumoral cell survival or for eliminating a tumoral cell in a mammal, comprising the step of reducing cellular expression levels of a SIMP polypeptide.
A method for modulating an immune response in a mammal, comprising increasing in lymphoid cells of said mammals the cellular expression levels of a SIMP polypeptide.
A method for decreasing lymphoid cells proliferation, comprising decreasing in said cells cellular expression levels of a SIMP polypeptide.
A nucleotide probe comprising a sequence of at least 15 sequential nucleotides of SEQ ID NO:
- 1 or of a sequence complementary to SEQ ID NO:
- 1.
A substantially pure nucleic acid that hybridizes to a probe of at least 40 nucleotides in length, said probe derived from SEQ ID NO:1, wherein said nucleic acid hybridizes to said probe under high stringency conditions.
A purified antibody that specifically binds to a purified mammalian SIMP polypeptide.
A method of diagnosis of a cancer in a human subject comprising the step of determining the amount of a human SIMP polypeptide in a cell or a biological sample from said subject, wherein said amount is indicative of a probability for said subject of harboring proliferating tumoral cells.
The method of 75, wherein said proliferating tumoral cells grow rapidly and display a short doubling time.
The method of 75, wherein said cancer is selected from the group consisting of:
- lung cancers, intestine cancers, sarcomas, prostate cancer, testis cancer, breast cancer, melanomas, pancreatic cancer and hematologic cancers.
A method for producing a human SIMP polypeptide comprising:
- providing a cell transformed with a nucleic acid sequence encoding a human SIMP polypeptide positioned for expression in said cell;
- culturing said transformed cell under conditions suitable for expressing said nucleic acid;
- and
- producing said hSIMP polypeptide.
Dependencies are inferred from the claim text.