THERAPEUTIC COMPOSITIONS AND METHODS FOR TREATING DISEASE STATES WITH MYELOID PROGENITOR INHIBITORY FACTOR-1 (MPIF-1), MONOCYTE COLONY INHIBITORY FACTOR (M-CIF), AND MACROPHAGE INHIBITORY FACTOR-4 (MIP-4)

摘要

PURPOSE: Provided are therapeutic compositions and methods using isolated nucleic acid molecules encoding a human myeloid progenitor inhibitory factor-1 (MPIF-1) polypeptide (previously termed MIP-3 and chemokine beta 8 (CK beta 8 or ckb-8)); a human monocyte-colony inhibitory factor (M-CIF) polypeptide (previously termed MIP1- gamma and chemokine beta 1(CK beta 1 or ckb-1)), and a macrophage inhibitory protein-4 (MIP-4), as well as MPIF-1, M-CIF and/or MIP-4 polypeptides themselves, as are vectors, host cells and recombinant methods for producing the same. CONSTITUTION: A method of inhibiting proliferation or differentiation of myeloid progenitor cells, comprising administering to an individual an effective amount of a polypeptide selected from the group consisting of: (a) a Myeloid Progenitor Inhibitory Factor (MPIF- 1) N-terminal deletion mutant comprising an amino acid sequence of SEQ ID NO:4 having a deletion of at least the first 22 N-terminal amino acid residues but not more than the first 53 Nterminal amino acid residues of SEQ ID NO:4; (b) a MPIF-1 C-terminal deletion mutant comprising an amino acid sequence of SEQ ID NO:4 having a deletion of at least the last C-terminal amino acid residue but not more than the last 52 C-terminal amino acid residues of SEQ ID NO: 4, wherein the N-terminal amino acid residue of said MPIF-I C-terminal deletion mutant is amino acid residue 1 (Met) or 22 (Arg) of SEQ ID NO:4; (c) a MPIF-I N-terminal and C-terminal deletion mutant comprising an amino acid sequence of SEQ ID NO:4 having a deletion of at least the first 22 Nterminal amino acid residues but not more than the first 53 N-terminal amino acid residues of SEQ ID NO:4 and a deletion of at least the last C-terminal amino acid residue but not more than the last 52 C-terminal amino acid residues of SEQ ID NO:4; (d) a polypeptide having an amino acid sequence at least 95% identical to the amino acid sequence of said MPIF-1 deletion mutant of (a); (e) a polypeptide having an amino acid sequence at least 95% identical to the amino acid sequence of said MPIF-I deletion mutant of(b); (f) a polypeptide having an amino acid sequence at least 95% identical to the amino acid sequence of said MPIF- 1 deletion mutant of (c); (g) a polypeptide having an amino acid sequence identical to the amino acid sequence of said MPIF- 1 deletion mutant of (a) except for at least one amino acid substitution; (h) a polypeptide having an amino acid sequence identical to the amino acid sequence of said MPIF- 1 deletion mutant of (b) except for at least one amino acid substitution; and (i) a polypeptide having an amino acid sequence identical to the amino acid sequence of said MPIF- 1 deletion mutant of (c) except for at least one amino acid substitution.