CONJUGATE VACCINE USING TRIMMING FUNCTION OF ERAP1

1 . A compound represented by formula (1):

or a pharmaceutically acceptable salt thereof,

wherein X a and Y a are each independently a single bond or a divalent peptide group consisting of 1-4 amino acid residues, and a total of the amino acid residue number for X a and the amino acid residue number for Y a is an integer of 0-4,

cancer antigen peptide A is an MHC class I-restricted cancer antigen peptide consisting of 7-30 amino acid residues, an amino group of an N-terminal amino acid of the cancer antigen peptide A binds to Y a in the formula (1), and a carbonyl group of a C-terminal amino acid of the cancer antigen peptide A binds to a hydroxyl group in the formula (i), and

R 1 is a hydrogen atom;

a group represented by formula (3):

wherein X c and Y c are each independently a single bond or a divalent peptide group consisting of 1-4 amino acid residues, and a total of the amino acid residue number for X c and the amino acid residue number for Y c is an integer of 0-4,

cancer antigen peptide C is an MHC class II-restricted cancer antigen peptide consisting of 7-30 amino acid residues, a carbonyl group of a C-terminal amino acid of the cancer antigen peptide C binds to X c in the formula (3), and an amino group of an N-terminal amino acid of the cancer antigen peptide C binds to a hydrogen atom in the formula (3), and

a thioether group in the formula (3) binds to a thioether group in the formula (1);

or cancer antigen peptide D, wherein the cancer antigen peptide D is an MHC class I-restricted cancer antigen peptide consisting of 7-30 amino acid residues containing one cysteine residue or an MHC class II-restricted cancer antigen peptide consisting of 7-30 amino acid residues containing one cysteine residue, and a thioether group of the cysteine residue of the cancer antigen peptide D binds to a thioether group in the formula (1),

provided when R 1 is a hydrogen atom, the sequence of the formula (1) is not identical to the partial sequence of a cancer antigen protein.

2 . The compound of claim 1 , wherein X a is a single bond, and Y a is a single bond, an alanine residue, a leucine residue or a methionine residue,

or a pharmaceutically acceptable salt thereof.

3 . The compound of claim 1 , wherein X a is a single bond, an alanine residue, a glycine residue, a serine residue or a tyrosine residue, and Y a is a single bond,

or a pharmaceutically acceptable salt thereof.

4 . The compound of claim 1 , wherein X a and Y a are each a single bond,

or a pharmaceutically acceptable salt thereof.

5 . The compound of claim 1 , wherein the cancer antigen peptide A is a peptide consisting of an amino acid sequence selected from SEQ ID NOs: 1-85, 87 and 88,

the cancer antigen peptide C is a peptide consisting of an amino acid sequence selected from SEQ ID NOs: 101 and 102, the cancer antigen peptide D is a peptide consisting of an amino acid sequence selected from SEQ ID NOs: 3, 26, 37, 39, 56, 69, 70, 72, 75, 83, 84, 87 and 88, or a peptide consisting of an amino acid sequence selected from SEQ ID NOs: 103, 104, 105, 106 and 107,

or a pharmaceutically acceptable salt thereof.

6 . The compound of claim 1 , wherein the cancer antigen peptide A is a peptide consisting of an amino acid sequence selected from SEQ ID NOs: 3, 11, 13, 19, 26, 27, 29, 33, 40, 41, 43, 50, 53, 66, 83, 84, 85, 87 and 88,

or a pharmaceutically acceptable salt thereof.

7 . The compound of claim 1 , wherein the cancer antigen peptide A is a peptide consisting of an amino acid sequence selected from the following amino acid sequences:

(SEQ ID NO: 19)

GLYDGMEHL,

(SEQ ID NO: 43)

VLQELNVTV and

(SEQ ID NO: 53)

KIFGSLAFL,

or a pharmaceutically acceptable salt thereof.

8 . The compound of claim 1 , wherein R 1 is a hydrogen atom, or a pharmaceutically acceptable salt thereof.

9 . The compound of claim 1 , wherein the compound is a peptide consisting of an amino acid sequence selected from SEQ ID NOs: 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 108, 111, 112, 114, 115, 116, 117, 119, 120, 121, 122 and 123,

or a pharmaceutically acceptable salt thereof.

10 . The compound of claim 1 , wherein R 1 is a group represented by the formula (3),

or a pharmaceutically acceptable salt thereof.

11 . The compound of claim 1 , wherein X c and Y c are each a single bond,

or a pharmaceutically acceptable salt thereof.

12 . The compound of claim 1 , wherein the cancer antigen peptide C is a peptide consisting of an amino acid sequence selected from the following amino acid sequences:

(SEQ ID NO: 101)

AKFVAAWTLKAAA and

(SEQ ID NO: 102)

aKFVAAWTLKAAa,

or a pharmaceutically acceptable salt thereof.

13 . The compound of claim 1 , wherein R 1 is cancer antigen peptide D,

or a pharmaceutically acceptable salt thereof.

14 . The compound of claim 1 , wherein the cancer antigen peptide D is a peptide consisting of an amino acid sequence selected from SEQ ID NOs: 3, 26, 37, 39, 56, 69, 70, 72, 75, 83, 84, 87 and 88, or a peptide consisting of an amino acid sequence selected from SEQ ID NOs: 103, 104, 105, 106 and 107,

or a pharmaceutically acceptable salt thereof.

15 . The compound of claim 1 , wherein the cancer antigen peptide D is a peptide consisting of an amino acid sequence selected from the following amino acid sequences:

(SEQ ID NO: 87)

VYGFVRACL and

(SEQ ID NO: 88)

SLLMWITQC,

or a pharmaceutically acceptable salt thereof.

16 . The compound of claim 1 , wherein the cancer antigen peptide D is a peptide consisting of the following amino acid sequence:

(SEQ ID NO: 103)

aK-Cha-VAAWTLKAAa-Ahx-C,

or a pharmaceutically acceptable salt thereof.

17 . The compound of claim 1 , wherein the cancer antigen peptide D is a peptide consisting of an amino acid sequence selected from the following amino acid sequences:

(SEQ ID NO: 104)

AADHRQLQLSISSCLQQL,

(SEQ ID NO: 105)

RNGYRALMDKSLHVGTQCALTRR,

(SEQ ID NO: 106)

KKLQCVQLHVISM and

(SEQ ID NO: 107)

GSYVSRLLGICL,

or a pharmaceutically acceptable salt thereof.

18 . A pharmaceutical composition, comprising:

the compound of claim 1 or a pharmaceutically acceptable salt thereof; and

a pharmaceutically acceptable carrier.

19 . A method of treating or preventing cancer, comprising administering a therapeutically or prophylactically effective amount of the compound of claim 1 or a pharmaceutically acceptable salt thereof to a cancer patient positive for a cancer antigen protein in need thereof.