Immunity-inducing agent and pharmaceutical composition containing same
Disclosed is an immunity-inducing agent having excellent ease of production and high immunostimulatory activity, the immunity-inducing agent comprising, as an active component, a polynucleotide/peptide conjugate in which an antigenic peptide is covalently bound to a single-stranded polynucleotide or polynucleotide derivative. Also disclosed is a pharmaceutical composition comprising said immunity-inducing agent.
1. An immunity-inducing agent comprising, as an active component, a polynucleotide/peptide conjugate in which an antigenic peptide is covalently bound to a single-stranded polynucleotide or polynucleotide derivative, wherein the polynucleotide or polynucleotide derivative is a polydeoxycytidylic acid, a polydeoxythymidylic acid or a polydeoxyguanylic acid, and wherein the polynucleotide or polynucleotide derivative is not complexed with β-1,3-glucan.
2. The immunity-inducing agent according to claim 1 , wherein the antigenic peptide has an amino acid length of not less than 5 but not more than 30.
3. The immunity-inducing agent according to claim 1 , wherein the polynucleotide or polynucleotide derivative has a nucleotide length of not less than 20 but not more than 80.
4. The immunity-inducing agent according to claim 1 , wherein the polynucleotide or polynucleotide derivative is a polynucleotide derivative in which phosphodiester bonds are at least partially substituted with phosphorothioate groups.
5. The immunity-inducing agent according to claim 4 , wherein, in the polynucleotide derivative in which phosphodiester bonds are at least partially substituted with phosphorothioate groups, not less than 50% of the phosphodiester bonds are substituted with phosphorothioate groups.
6. The immunity-inducing agent according to claim 1 , wherein the antigenic peptide and the polynucleotide or polynucleotide derivative, which constitute the polynucleotide/peptide conjugate, are bound together via covalent bonding produced by any of a cycloaddition reaction between alkyne and an azide derivative, and a reaction between a maleimide group and a thiol group.
7. The immunity-inducing agent according to claim 1 , wherein the antigenic peptide and the polynucleotide or polynucleotide derivative, which constitute the polynucleotide/peptide conjugate, are bound together via covalent bonding produced by a reaction between a thiol group of a cysteine residue at the N-terminus of the peptide and a thiol group of a thiol-modified nucleic acid.
8. The immunity-inducing agent according to claim 1 , further comprising a substance having immunostimulatory activity as an adjuvant.
9. The immunity-inducing agent according to claim 8 , wherein the adjuvant is a polynucleotide or polynucleotide derivative containing a partial nucleotide sequence having immunostimulatory activity.
10. A pharmaceutical composition comprising the immunity-inducing agent according to claim 1 .
11. The immunity-inducing agent according to claim 1 , wherein
the antigenic peptide has an amino acid length of not less than 5 but not more than 30;
the polynucleotide or polynucleotide derivative has a nucleotide length of not less than 20 but not more than 80;
the polynucleotide or polynucleotide derivative is a polynucleotide derivative in which phosphodiester bonds are at least partially substituted with phosphorothioate groups, wherein in said polynucleotide derivative, not less than 50% of the phosphodiester bonds are substituted with phosphorothioate groups;
the antigenic peptide and the polynucleotide or polynucleotide derivative, which constitute the polynucleotide/peptide conjugate, are bound together via covalent bonding produced by any of a cycloaddition reaction between alkyne and an azide derivative, and a reaction between a maleimide group and a thiol group; and
further comprising a substance having immunostimulatory activity as an adjuvant.
12. The immunity-inducing agent according to claim 1 , wherein
the antigenic peptide has an amino acid length of not less than 5 but not more than 30;
the polynucleotide or polynucleotide derivative has a nucleotide length of not less than 20 but not more than 80;
the polynucleotide or polynucleotide derivative is a polynucleotide derivative in which phosphodiester bonds are at least partially substituted with phosphorothioate groups, wherein, in said polynucleotide derivative, not less than 50% of the phosphodiester bonds are substituted with phosphorothioate groups;
the antigenic peptide and the polynucleotide or polynucleotide derivative, which constitute the polynucleotide/peptide conjugate, are bound together via covalent bonding produced by a reaction between a thiol group of a cysteine residue at the C-terminus of the peptide and a thiol group of a thiol-modified nucleic acid; and
further comprising a substance having immunostimulatory activity as an adjuvant.
13. A pharmaceutical composition comprising the immunity-inducing agent according to claim 11 .
14. A pharmaceutical composition comprising the immunity-inducing agent according to claim 12 .