Partial Region Polypeptide of REIC/Dkk-3 Protein
A polypeptide capable of strongly inducing and activating dendritic-cell-like cells for treating or prevent cancer by immunotherapy, and DNA encoding the polypeptide. The polypeptide is a polypeptide (a) or (b) consisting of a partial region of the REIC/Dkk-3 protein.
1 . A polypeptide that is any one of the following polypeptides (a) to (e), which consists of a partial region of a REIC/Dkk-3 protein:
(a) a polypeptide consisting of a partial region of the REIC/Dkk-3 protein, which consists of an amino acid sequence selected from the group consisting of
the amino acid sequences shown in SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 7 and SEQ ID NO: 9, and
the amino acid sequence of a polypeptide that contains the partial region consisting of Gly at position 205 to Phe at position 288 of the amino acid sequence shown in SEQ ID NO: 2, and consists of a fragment of the partial region consisting of Ser at position 135 to Ile at position 350 of the amino acid sequence shown in SEQ ID NO: 2;
(b) a polypeptide having activity of inducing dendritic-cell-like cell differentiation from monocytes, which is a polypeptide protein consisting of an amino acid sequence that has a substitution, a deletion, or an addition of 1 or several amino acids with respect to an amino acid sequence selected from the group consisting of
the amino acid sequences shown in SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 7 and SEQ ID NO: 9, and
the amino acid sequence of a polypeptide that contains the partial region consisting of Gly at position 205 to Phe at position 288 of the amino acid sequence shown in SEQ ID NO: 2, and consists of a fragment of the partial region consisting of Ser at position 135 to Ile at position 350 of the amino acid sequence shown in SEQ ID NO: 2;
(c) a polypeptide consisting of a partial region of the REIC/Dkk-3 protein, which can bind to a Tctex-1 protein and consists of the amino acid sequence shown in SEQ ID NO: 17, and;
(d) a polypeptide consisting of an amino acid sequence having a substitution, a deletion, or an addition of 1 or several amino acids with respect to the amino acid sequence shown in SEQ ID NO: 17 and having the activity of binding to the Tctex-1 protein; and
(e) a polypeptide consisting of a partial region of the REIC/Dkk-3 protein and being capable of binding to the Tctex-1 protein, which contains the consensus sequence shown in SEQ ID NO: 18 and consists of 7 to 22 amino acid residues.
2 . DNA that is any one of the following DNAs (f) to (l), which encodes a polypeptide consisting of a partial region of a REIC/Dkk-3 protein;
(f) DNA consisting of a nucleotide sequence selected from the group consisting of
the nucleotide sequences shown in SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 8 and SEQ ID NO: 10, and
a nucleotide sequence that contains the partial sequence consisting of g at position 613 to c at position 864 of the nucleotide sequence shown in SEQ ID NO: 1, and consists of a fragment of the partial sequence consisting of t at position 403 to t at position 1050 of the nucleotide sequence shown in SEQ ID NO: 1;
(g) DNA hybridizing under stringent conditions to DNA consisting of a nucleotide sequence complementary to a nucleotide sequence selected from the group consisting of
the nucleotide sequences shown in SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 8 and SEQ ID NO: 10, and
a nucleotide sequence that contains the partial sequence consisting of g at position 613 to c at position 864 of the nucleotide sequence shown in SEQ ID NO: 1, and consists of a fragment of the partial sequence consisting of t at position 403 to t at position 1050 of the nucleotide sequence shown in SEQ ID NO: 1, and encoding a polypeptide having activity of inducing dendritic-cell-like cell differentiation from monocytes;
(h) DNA consisting of a nucleotide sequence having a deletion, a substitution, or an addition of 1 or several nucleotides with respect to a nucleotide sequence selected from the group consisting of
the nucleotide sequences shown in SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 8 and SEQ ID NO: 10, and
a nucleotide sequence that contains the partial sequence consisting of g at position 613 to c at position 864 of the nucleotide sequence shown in SEQ ID NO: 1, and consists of a fragment of the partial sequence consisting of t at position 403 to t at position 1050 of the nucleotide sequence shown in SEQ ID NO: 1, and encoding a polypeptide having activity of inducing dendritic-cell-like cell differentiation from monocytes;
(i) DNA consisting of a DNA sequence that encodes an amino acid sequence selected from the group consisting of
the amino acid sequences shown in SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 7 and SEQ ID NO: 9, and
the amino acid sequence of a polypeptide that contains the partial region consisting of Gly at position 205 to Phe at position 288 of the amino acid sequence shown in SEQ ID NO: 2, and consists of a fragment of the partial region consisting of the Ser at position 135 to Ile at position 350 of the amino acid sequence shown in SEQ ID NO: 2, and
encoding a polypeptide having activity of inducing dendritic-cell-like cell differentiation from monocytes;
(j) DNA encoding a polypeptide that consists of a partial region of the REIC/Dkk-3 protein and is capable of binding to the Tctex-1 protein, which consists of the nucleotide sequence consisting of g at position 4 to g at position 69 of the nucleotide sequence shown in SEQ ID NO: 8;
(k) DNA hybridizing under stringent conditions to DNA consisting of a nucleotide sequence complementary to the nucleotide sequence consisting of g at position 4 to g at position 69 of the nucleotide sequence shown in SEQ ID NO: 8, and encoding a polypeptide having activity of binding to the Tctex-1 protein; and
(l) DNA encoding a polypeptide that consists of a partial region of the REIC/Dkk-3 protein, is capable of binding to the Tctex-1 protein, consists of the DNA sequence encoding the amino acid sequence shown in SEQ ID NO: 17, and has activity of binding to the Tctex-1 protein.
3 . A vector, containing the DNA of claim 2 .
4 . The vector according to claim 3 , wherein the vector is an adenovirus vector.
5 . An agent for inducing dendritic-cell-like cell differentiation from monocytes, containing the polypeptide of claim 1 consisting of a partial region of the REIC/Dkk-3 protein as an active ingredient.
6 . An agent for accelerating the induction of differentiation to immunoactivation cells selected from the group consisting of dendritic cells, helper T cells, CTL, and NK cells, containing the polypeptide of claim 1 consisting of a partial region of the REIC/Dkk-3 protein as an active ingredient.
7 . An agent for inhibiting the induction of differentiation to immunosuppressively functioning cells that are myeloid-derived suppressor cells (MDSC) or immunoregulatory T cells (Treg), containing the polypeptide of claim 1 consisting of a partial region of the REIC/Dkk-3 protein as an active ingredient.
8 . An anticancer agent, containing the polypeptide of claim 1 consisting of a partial region of the REIC/Dkk-3 protein as an active ingredient.
9 . An agent for inducing dendritic-cell-like cell differentiation from monocytes, containing the DNA of claim 2 that encodes the polypeptide consisting of a partial region of the REIC/Dkk-3 protein or the vector of claim 3 as an active ingredient.
10 . An agent for accelerating the induction of differentiation to immunoactivation cells selected from the group consisting of dendritic cells, helper T cells, CTL, and NK cells, containing the DNA of claim 2 encoding the polypeptide consisting of a partial region of the REIC/Dkk-3 protein or the vector of claim 3 as an active ingredient.
11 . An agent for inhibiting the induction of differentiation to immunosuppressive cells that are myeloid-derived suppressor cells (MDSC) or immunoregulatory T cells (Treg), containing the DNA of claim 2 encoding the polypeptide consisting of a partial region of the REIC/Dkk-3 protein or the vector of claim 3 as an active ingredient.
12 . An anticancer agent, containing the DNA of claim 2 encoding the polypeptide consisting of a partial region of the REIC/Dkk-3 protein or the vector of claim 3 as an active ingredient.
13 . A method for inducing dendritic-cell-like cell differentiation from CD14 positive monocytes, comprising culturing monocytes collected from an animal in vitro in the presence of the polypeptide of claim 1 consisting of a partial region of the REIC/Dkk-3 protein.
14 . The method according to claim 13 , wherein the monocytes are peripheral blood monocytes.