Combination use of wt1 antigen peptide and immunomodulator

Patent metadata

Field	Value
Publication number	US-2024293521-A1
Application number	US-202318538960-A
Country	US
Kind code	A1
Filing date	Dec 13, 2023
Priority date	May 20, 2015
Publication date	Sep 5, 2024
Grant date	—

Abstract

The invention relates to a combination use of a WT1 antigen peptide or a pharmaceutically acceptable salt thereof and an immunomodulator for treating or preventing cancer.

First claim

1 . A method for treating or preventing cancer, comprising administering a WT1 antigen peptide or a pharmaceutically acceptable salt thereof and an immunomodulator to a mammal, wherein the WT1 antigen peptide is a WT1 killer peptide and the WT1 killer peptide or a pharmaceutically acceptable salt thereof is:
a peptide consisting of an amino acid sequence selected from the group consisting of RMFPNAPYL (SEQ ID NO: 2), CMTWNQMNL (SEO ID NO: 3, CYTWNQMNL (SEQ ID NO: 4), ALLPAVPSL (SEQ ID NO: 5), SLGEQQYSV (SEQ ID NO: 6), RVPGVAPTL (SEQ ID NO: 7), VLDFAPPGA, (SEQ ID NO: 8), C—CMTWNQMNL (SEO ID NO: 9) wherein the C—C bond is a disulfide bond, C—CYTWNQMNL (SEQ ID NO: 10) wherein the C—C bond is a disulfide bond, RYFPNAPYL (SEO ID NO: 21), and YMFPNAPYL (SEQ ID NO: 26); a peptide comprising an altered amino acid sequence relative to an amino acid sequence selected from the group consisting of SEQ ID NOS: 2-10, 21 and 26 that comprises deletion, substitution, or addition of one to several amino acids in the amino acid sequence and having a CTL induction activity; or a compound selected from the group consisting of: the compound of formula (I):

wherein the C—C bond is a disulfide bond,
the compound of formula (2):

wherein the C—C bond is a disulfide bond, and
the compound of formula (3):

wherein the C—C bond is a disulfide bond;
or a pharmaceutically acceptable salt thereof, and
the immunomodulator is at least one agent selected from the group consisting of
(1) an immune checkpoint inhibitor which is at least one agent directed to a molecule selected from the group consisting of
CTLA-4,
LAG-3,
BTLA,
KIR,
TIM-3,
PD-L1,
PD-L2,
B7-H3,
B7-H4,
HVEM,
GAL9,
CD160,
VISTA,
BTNL2,
TIGIT,
PVR,
BTN1A1,
BTN2A2,
BTN3A2, and
CSF-1R,
(2) a costimulatory molecule agonist which is at least one agent directed to a molecule selected from the group consisting of
4-1BB,
4-1BB-L,
OX40,
OX40-L,
GITR,
CD28,
CD40-L,
ICOS,
ICOS-L,
LIGHT, and
CD27,
(3) an immune activating agent wherein the immune activating agent is a Toll-like receptor (TLR) agonist which is at least one agent selected from the group consisting of
a TLR1/2 agonist,
a TLR2 agonist,
a TLR3 agonist,
a TLR4 agonist,
a TLR5 agonist,
a TLR6/2 agonist,
a TLR7 agonist,
a TLR7/8 agonist,
a TLR7/9 agonist,
a TLR8 agonist,
a TLR9 agonist, and
a TLR11 agonist, and
(4) a low-molecular inhibitor which is an agent selected from the group consisting of a β-catenin inhibitor, a IDO inhibitor, a COX-2 inhibitor, a CXCR4 inhibitor, a STAT3 inhibitor, and a multikinase inhibitor.

2 . (canceled)

3 . The method of claim 1 , wherein the WT1 killer peptide or a pharmaceutically acceptable salt thereof is:
a peptide consisting of an amino acid sequence selected from the group consisting of RMFPNAPYL (SEQ ID NO: 2), CMTWNQMNL (SEQ ID NO: 3), CYTWNQMNL (SEQ ID NO: 4), ALLPAVPSL (SEQ ID NO: 5), C—CYTWNQMNL (SEQ ID NO: 10) wherein the C—C bond is a disulfide bond, and YMFPNAPYL (SEQ ID NO: 26); or a pharmaceutically acceptable salt thereof.

4 . The method of claim 1 , wherein the WT1 killer peptide or a pharmaceutically acceptable salt thereof is:
the compound of formula (3):

wherein the C—C bond is a disulfide bond:
or a pharmaceutically acceptable salt thereof.

5 . The method of claim 1 , further comprising administering a WT1 helper peptide or a pharmaceutically acceptable salt thereof, wherein the WT1 helper peptide or a pharmaceutically acceptable salt thereof is
a peptide consisting of an amino acid sequence selected from the group consisting of KRYFKLSHLQMHSRKH (SEQ ID NO: 11), SGQARMFPNAPYLPSCLES (SEQ ID NO: 12), RSDELVRHHNMHQRNMTKL (SEQ ID NO: 13), PGCNKRYFKLSHLQMHSRKHTG (SEQ ID NO: 14), CNKRYFKLSHLQMHSRK (SEQ ID NO: 15), CNKRYFKLSHLQMHSRKH (SEQ ID NO: 16), CNKRYFKLSHLQMHSRKHTG (SEQ ID NO: 17), WAPVLDFAPPGASAYGSL (SEQ ID NO: 18), CWAPVLDFAPPGASAYGSL (SEQ ID NO: 19), WAPVLDFAPPGASAYGSLC (SEQ ID NO: 20), and SGQAYMFPNAPYLPSCLES (SEQ ID NO: 37); or a peptide comprising an altered amino acid sequence relative to an amino acid sequence selected from the group consisting of SEQ ID NOS: 11-20 and 37 that comprises deletion, substitution, or addition of one to several amino acids in the amino acid sequence and having a helper T cell induction activity; or a pharmaceutically acceptable salt thereof.

6 . The method of claim 5 , wherein the WT1 helper peptide or a pharmaceutically acceptable salt thereof is a peptide consisting of an amino acid sequence of
WAPVLDFAPPGASAYGSL (SEQ ID NO: 18), or a pharmaceutically acceptable salt thereof.

7 . (canceled)

8 . The method of claim 1 , wherein the immunomodulator is an antibody, a nucleic acid molecule, a protein, a peptide or a low molecular compound.

9 . The method of claim 1 , wherein the immunomodulator is the immune checkpoint inhibitor.

10 . (canceled)

11 . The method of claim 9 , wherein the immune checkpoint inhibitor is at least one agent directed to a molecule selected from the group consisting of CTLA-4, PD-1, LAG-3, TIM-3, BTLA, VISTA, HVEM, TIGIT, PVR, PD-L1 and CD160.

12 . The method of claim 11 , wherein the immune checkpoint inhibitor is an agent directed to PD-1 or PD-L1.

13 . The method of claim 12 , wherein the immune checkpoint inhibitor is an antibody against PD-1 or PD-L1.

14 . The method of claim 13 , wherein the antibody against PD-1 is Nivolumab or Pembrolizumab.

15 . The method of claim 13 , wherein the antibody against PD-L1 is Durvalumab, MPDL3280A or BMS-936559.

16 . The method of claim 1 , wherein the immunomodulator is the costimulatory molecule agonist.

17 . (canceled)

18 . The method of claim 16 , wherein the costimulatory molecule agonist is at least one agent directed to a molecule selected from the group consisting of 4-1BB, OX40, GITR, CD40 and ICOS.

19 . The method of claim 1 , wherein the immunomodulator is the immune activating agent.

20 . (canceled)

21 . (canceled)

22 . The method of claim 19 , wherein the TLR agonist is at least one agent selected from the group consisting of a TLR3 agonist, a TLR7 agonist, a TLR7/8 agonist, and a TLR9 agonist.

23 . The method of claim 1 , wherein the immunomodulator is the low-molecular inhibitor.

24 . (canceled)

25 . The method of claim 23 , wherein the low-molecular inhibitor is a β-catenin inhibitor.

26 . The method of claim 1 , wherein the cancer is selected from the group consisting of leukemia, myelodysplastic syndrome, mul

Assignees

• Sumitomo Pharma Co Ltd
• Int Inst Cancer Immunology Inc

Inventors

• Takasu Hideo
• Nakamura Megumi
• Goto Masashi
• Suginobe Natsuko

Classifications

• A61K2039/545

  characterised by the dose, timing or administration schedule · CPC title

• A61K2039/505

  comprising antibodies · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61K39/001153 Primary

  Wilms tumor 1 [WT1] · CPC title

• A61K39/395

  Antibodies (agglutinins A61K38/36 {; as drug carriers A61K47/50}); Immunoglobulins; Immune serum, e.g. antilymphocytic serum · CPC title