Immunogenic wt-1 peptides and methods of use thereof

Patent metadata

Field	Value
Publication number	US-2017334951-A1
Application number	US-201715608964-A
Country	US
Kind code	A1
Filing date	May 30, 2017
Priority date	Jan 13, 2012
Publication date	Nov 23, 2017
Grant date	—

Abstract

This invention provides peptides, immunogenic compositions and vaccines, and methods of treating, reducing the incidence of, and inducing immune responses to a WT-1-expressing cancer, comprising peptides derived from the WT-1 protein.

First claim

1 . An isolated WT-1 peptide consisting of an amino acid sequence selected from among AILDFLLLQ (SEQ ID NO:147), RQRPHPGAL (SEQ ID NO:142), GALRNPTAC (SEQ ID NO:143), THSPTHPPR (SEQ ID NO:146), WNQMNLGATLK (SEQ ID NO:173), PGCLQQPEQQG (SEQ ID NO:149), LDFAPPGASAY (SEQ ID NO:156), PLPHFPPSL (SEQ ID NO:144), HFPPSLPPT (SEQ ID NO:145), LLAAILDFL (SEQ ID NO:184), CLQQPEQQGV (SEQ ID NO:185), ALRNPTACPL (SEQ ID NO:191), GGCALPVSGA (SEQ ID NO:153), LGATLKGVAA (SEQ ID NO:176), TLGVAAGS (SEQ ID NO:177), KRPFMCAYPGC (SEQ ID NO:180) LKTHTRTHT (SEQ ID NO:182) and SEQ ID NOS:1-15.

2 - 4 . (canceled)

5 . An isolated WT-1 peptide consisting of 8-30 amino acids comprising an amino acid sequence selected from SEQ ID NO: 142, 143, 144, 145, 146, 147, 149 and 184.

6 . An isolated WT-1 peptide consisting of 16-30 amino acids comprising an amino acid sequence selected from SEQ ID NO:1-15.

7 . The isolated WT-1 peptide of claim 1 or 5 , wherein said isolated WT-1 peptide can bind to an HLA class I molecule, an HLA class II molecule, or the combination thereof.

8 . A pharmaceutical composition comprising one or more peptides of claim 1 or 5 and a pharmaceutically acceptable carrier, vehicle or excipient.

9 . A vaccine comprising (a) one or more isolated WT-1 peptides of claim 1 or 5 and (b) an adjuvant or a carrier.

10 . The vaccine of claim 9 , wherein said adjuvant is QS21, Freund's incomplete adjuvant, aluminum phosphate, aluminum hydroxide, BCG, alum, a growth factor, a cytokine, a chemokine, an interleukin, Montanide or GM-CSF.

11 . A method of treating a subject with a WT-1-expressing cancer or reducing an incidence of a WT-1-expressing cancer, or its relapse, the method comprising administering to said subject one or more peptides of any one of claim 1 , 5 or 6 , a composition thereof, a composition thereof further comprising an antigen presenting cell, or a vaccine thereof or any combination thereof, thereby treating a subject with a WT-1-expressing cancer, reducing an incidence of a WT-1-expressing cancer or its relapse therein.

12 . The method of claim 11 , wherein said WT-1-expressing cancer is a leukemia, a desmoplastic small round cell tumor, a gastric cancer, a colon cancer, a lung cancer, a breast cancer, a germ cell tumor, an ovarian cancer, a uterine cancer, a thyroid cancer, a liver cancer, a renal cancer, a Kaposi's sarcoma, a sarcoma, a hepatocellular carcinoma, a Wilms' tumor, an acute myelogenous leukemia (AML), a myelodysplastic syndrome (MDS), mesothelioma or a non-small cell lung cancer (NSCLC).

13 . A method of inducing the formation and proliferation of CTL specific for cells of a WT-1-expressing cancer, the method comprising administering to said subject one or more peptides of any one of claim 1 , 5 or 6 , a composition thereof or a vaccine thereof or any combination thereof, thereby inducing the formation and proliferation of CTL specific for cells of a WT-1-expressing cancer.

14 . The method of claim 13 , wherein said WT-1-expressing cancer is a leukemia, a desmoplastic small round cell tumor, a gastric cancer, a colon cancer, a lung cancer, a breast cancer, a germ cell tumor, an ovarian cancer, a uterine cancer, a thyroid cancer, a liver cancer, a renal cancer, a kaposi's sarcoma, a sarcoma, a hepatocellular carcinoma, a Wilms' tumor, an acute myelogenous leukemia (AML), a myelodysplastic syndrome (MDS), mesothelioma or a non-small cell lung cancer (NSCLC).

15 . A composition comprising (a) an antigen-presenting cell and (b) one or more peptides of claim 1 or 5 .

16 . The vaccine of claim 9 further comprising a cell population xx.

17 . The composition of claim 15 wherein the antigen-presenting cell is a dendritic cell, monocyte, macrophage, cytokine-activated monocyte or an EBV-transformed B-lymphoblastoid cell.

18 . The composition of claim 15 wherein the antigen-presenting cell is from a cell line.

19 . The vaccine of claim 16 wherein the cell population is selected from lymphocytes, monocytes, macrophages, dendritic cells, endothelial cells, stem cells or any combination thereof.

20 . The vaccine of claim 16 wherein the cell population is autologous, syngeneic or allogeneic.

21 . The vaccine of claim 16 wherein the population is obtained from peripheral blood, leukopheresis blood product, apheresis blood product, peripheral lymph nodes, gut associated lymphoid tissue, spleen, thymus, cord blood, mesenteric lymph nodes, liver, a site of immunologic lesions, pancreas, cerebrospinal fluid, a tumor sample, or granulomatous tissue.

22 . A method of inducing formation and proliferation of WT1 protein-specific cytotoxic T lymphocytes comprising contacting a lymphocyte population in vitro or ex vivo with one or more peptides selected from AILDFLLLQ (SEQ ID NO:147), RQRPHPGAL (SEQ ID NO:142), GALRNPTAC (SEQ ID NO:143), THSPTHPPR (SEQ ID NO:146), PGCLQQPEQQG (SEQ ID NO:149), LDFAPPGASAY (SEQ ID NO:156), PLPHFPPSL (SEQ ID NO:144), HFPPSLPPT (SEQ ID NO:145), LLAAILDFL (SEQ ID NO:184), ALRNPTACPL (SEQ ID NO:191), GGCALPVSGA (SEQ ID NO:153), WNQMNLGATLK (SEQ ID NO:173), LGATLKGVAA (SEQ ID NO:176), TLGVAAGS (SEQ ID NO:177), KRPFMCAYPGC (SEQ ID NO:180), LKTHTRTHT (SEQ ID NO:182), and SEQ ID NOS:1-15; or an isolated WT1 peptide consisting of 8-30 amino acids comprising an amino acid sequence selected from SEQ ID NO: 142, 143, 144, 145, 146, 147, 149, and 184; or an isolated WT1 peptide consisting of 16-30 amino acids comprising an amino acid sequence selected from SEQ ID NOS:1-15, a composition thereof, a composition thereof further comprising an antigen presenting cell, or a vaccine thereof, or any combination thereof, thereby inducing formation and proliferation of WT1 protein-specific cytotoxic T lymphocytes.

23 . The method of claim 22 wherein the peptide is a pool of peptides having SEQ ID NOS:1-141.

24 . A method of treating a subject with a WT1-expressing cancer or reducing an incidence of a WT1-expressing cancer, or its relapse, the method comprising administering to said subject WT1 protein-specific cytotoxic T lymphocytes obtained by the method of claim 22 , thereby treating a subject with a WT1-expressing cancer, reducing an incidence of a WT1-expressing cancer or its relapse therein.

25 . The method of claim 24 wherein the peptide is a pool of peptides having SEQ ID NOS:1-141.

26 . A method of inducing formation and proliferation of (a) a WT1 protein-specific CD8+ lymphocyte; or (b) a CD4+ lymphocyte specific for the WT1 protein, or the combination thereof, the method comprising contacting a lymphocyte population in vitro or ex vivo with one or more peptides selected from AILDFLLLQ (SEQ ID NO:147), RQRPHPGAL (SEQ ID NO:142), GALRNPTAC (SEQ ID NO:143), THSPTHPPR (SEQ ID NO:146), PGCLQQPEQQG (SEQ ID NO:149), LDFAPPGASAY (SEQ ID NO:156), PLPHFPPSL (SEQ ID NO:144), HFPPSLPPT (SEQ ID NO:145), LLAAILDFL (SEQ ID NO:184), ALRNPTACPL (SEQ ID NO:191), GGCALPVSGA (SEQ ID NO:153), WNQMNLGATLK (SEQ ID NO:173), LGATLKGVAA (SEQ ID NO:176), TLGVAAGS (SEQ ID NO:177), KRPFMCAYPGC (SEQ ID NO:180), LKTHTRTHT (SEQ ID NO:182) and SEQ ID NOS:1-15; or an isolated WT1 peptide consisting of 8-30 amino acids comprising an amino acid sequence selected from SEQ ID NO: 142, 143, 144, 145, 146, 147, 149, and 184; or an isolated WT1 peptide consisting of 16-30 amino acids comprising an amino acid sequence selected from SEQ ID NOS:1-15, a composition thereof, a composition thereof further comprising an antigen presenting cell, or a vacc

Assignees

• Memorial Sloan Kettering Cancer Center

Inventors

• O'Reilly Richard J
• Doubrovina Ekaterina
• Selvakumar Annamalai

Classifications

• A61K2039/55522

  Cytokines; Lymphokines; Interferons · CPC title

• A61P35/02

  specific for leukemia · CPC title

• A61K2039/55516

  Proteins; Peptides · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• C07K7/08 Primary

  having 12 to 20 amino acids (gastrins C07K14/595; somatostatins C07K14/655; melanotropins C07K14/68) · CPC title