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AssigneeUniversity of Medicine and Dentistry of New Jersey
InventorPranela Rameshwar
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The present invention establishes the fact that the degradation of SP to SP(1-4) by endogenous NEP in BM stroma can be a mediator of hematopoietic stimulation by stem cell factor (SCF) and induce the production of TGF-β and TNF-α in BM stroma. The present invention establishes that compositions containing the SP(1-4) polypeptide, or NEP genetic elements, can be used to slow and or stop the rapid growth of stem and progenitor cells thus protecting them from the deleterious effects of cancer therapy. Hence, the polynucleotides and proteins of the present invention may be used to protect stem cells from the toxic effects of chemo- and radio-therapy, in those undergoing, or about to undergo such cancer related treatments. Also provided are compositions containing NEP antisense sequences and antibodies used for the increased proliferation and differentiation of stem and/or progenitor cells in those whom have already undergone chemo- and/or radio-therapy.
An isolated polynucleotide, comprising a nucleotide sequence that has at least 75% identity to SEQ ID NO:1 (coding for SP 1-4), said identity being calculated over the entire length of SEQ ID NO:1.
An isolated, purified SP (1-4) polypeptide.
A pharmaceutical composition comprising a biologically effective amount of a SP (1-4) polynucleotide or polypeptide and an acceptable carrier.
A pharmaceutical composition comprising a biologically effective amount of a NEP polynucleotide and an acceptable carrier.
A pharmaceutical composition comprising a biologically effective amount of a NEP polypeptide and an acceptable carrier.
A pharmaceutical composition comprising a biologically effective amount of an antibody immunospecific for the NEP protein comprising the amino acid sequence of SEQ ID NO:4, and an acceptable carrier.
A method of protecting stem cells in a subject about to undergo or undergoing cancer therapy, comprising the administration of a pharmaceutical composition comprising a biologically effective amount of a SP (1-4) polynucleotide or polypeptide and an acceptable carrier.
A method of protecting stem cells in a subject about to undergo or undergoing cancer therapy, comprising the administration of a pharmaceutical composition comprising a biologically effective amount of a NEP polynucleotide and an acceptable carrier.
A method of increasing stem cell growth, comprising the administration of a pharmaceutical composition comprising a biologically effective amount of a polynucleotide coding for the antisense sequence to SEQ. ID. No. 3, and an acceptable carrier.
A method of increasing stem cell growth, comprising the administration of a pharmaceutical composition comprising a biologically effective amount of an antibody immunospecific for the NEP polypeptide comprising the amino acid sequence of SEQ ID NO:4, and an acceptable carrier.
A vector for the delivery of a NEP therapeutic to a stem cell for the protection or rapid growth of stem cells, wherein the vector comprises an expression cassette encoding the NEP therapeutic.
A method for introducing a NEP therapeutic into a stem cell, comprising transfecting the cell with a plasmid comprising an expression cassette encoding the NEP therapeutic.
A method for increasing endogenous production of TGF-β or TNF-α, comprising the administration of a pharmaceutical composition comprising a biologically affective amount of a SP(1-4) polynucleotide or polypeptide and an acceptable carrier.
A method of protecting stem cells in a subject about to undergo or undergoing cancer therapy, comprising the administration of a pharmaceutical composition comprising a biologically effective amount of a NEP polypeptide and an acceptable carrier.
A vector for the delivery of a NEP therapeutic to a stem cell for the protection or rapid growth of stem cells, wherein the vector is selected from the goup consisting of a NEP polypeptide and an antibody immunospecific to the NEP protein.
A method for introducing a NEP polypeptide or an antibody immunospecific to the NEP protein into a stem cell, comprising transfecting the cell with a NEP polypeptide or antibody immunospecific to the NEP protein.
Dependencies are inferred from the claim text.