Partial Region Polypeptide of REIC/Dkk-3 Protein

Abstract

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.