WT1 HLA class II-binding peptides and compositions and methods comprising same

• US 10,221,224 B2
• Filed: 01/08/2016
• Issued: 03/05/2019
• Est. Priority Date: 10/17/2005
• Status: Active Grant

• Current Assignee: Memorial Sloan-Kettering Cancer Center
• Original Assignee: Memorial Sloan-Kettering Cancer Center
• Inventors: Scheinberg, David A., Pinilla-Ibarz, Javier, May, Rena
• Primary Examiner(s): Hill, Kevin K
• Assistant Examiner(s): Leonard, Arthur S
• Application Number:
  US14/991,442
• Publication Number:
  US 20160264638A1
• Time in Patent Office: 1,152 Days
• Field of Search: None
• CPC Class Codes: A61K 2039/57 characterised by the type of response, e.g. Th1, Th2
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61K 39/00 Medicinal preparations containing antigens or antibodies materials for immunoassay G01N33/53
• CPC Class Codes: A61K 39/001153 Wilms tumor 1 [WT1]
• CPC Class Codes: A61K 39/4611 T-cells, e.g. tumor infiltrating lymphocytes [TIL], lymphokine-activated killer cells [LAK] or regulatory T cells [Treg]
• CPC Class Codes: A61K 39/464453 Wilms tumor 1 [WT1]
• CPC Class Codes: A61K 39/464499 Undefined tumor antigens, e.g. tumor lysate or antigens targeted by cells isolated from tumor
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 37/04 Immunostimulants
• CPC Class Codes: C07K 14/4748 Tumour specific antigens; Tumour rejection antigen precursors [TRAP], e.g. MAGE

Abstract

This invention provides WT1 peptides and methods of treating, reducing the incidence of, and inducing immune responses against a WT1-expressing cancer, comprising same.

Claims

1. A nucleic acid encoding a Wilms tumor 1 (WT1) peptide consisting of the amino acid sequence RSDELVRHHNMHQRNMTKL (SEQ ID No:

2) or PGCNKRYFKLSHLQMHSRKHTG (SEQ ID No;

     4).

2. An expression vector comprising the nucleic acid of claim 1.

3. A method of inducing an anti-mesothelioma immune response in a subject, the method comprising the step of contacting said subject with the nucleic acid expression vector of claim 2, thereby inducing an anti-mesothelioma immune response in a subject.

4. A method of treating a subject with a mesothelioma, or reducing an incidence of a mesothelioma or its relapse, the method comprising the step of administering to said subject the nucleic acid expression vector of claim 2, thereby treating a subject with a mesothelioma, or reducing an incidence of a mesothelioma or its relapse.

5. A method of treating a subject with a WT1-expressing cancer, the method comprising administering to said subject the expression vector of claim 2, thereby treating a subject with a WT1-expressing cancer.

6. The method of claim 5, wherein said WT1-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, or a hepatocellular carcinoma.

7. The method of claim 5, wherein said WT1-expressing cancer is a Wilms'"'"' tumor, an acute myelogenous leukemia (AML), a myelodysplastic syndrome (MDS), a mesothelioma or a non-small cell lung cancer (NSCLC).

8. A method of reducing an incidence of a WT1-expressing cancer, or its relapse, in a subject, the method comprising administering to said subject the expression vector of claim 2, thereby reducing an incidence of a WT1-expressing cancer, or its relapse, in a subject.

9. The method of claim 8, wherein said WT1-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, or a hepatocellular carcinoma.

10. The method of claim 8, wherein said WT1-expressing cancer is a Wilms'"'"' tumor, an acute myelogenous leukemia (AML), a myelodysplastic syndrome (MDS), mesothelioma or a non-small cell lung cancer (NSCLC).

11. A method of inducing the formation and proliferation of CTL specific for cells of a WT1-expressing cancer, the method comprising administering to said subject the expression vector of claim 2, thereby inducing the formation and proliferation of CTL specific for cells of a WT1-expressing cancer.

12. The method of claim 11, wherein said WT1-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, or a hepatocellular carcinoma.

13. The method of claim 11, wherein said WT1-expressing cancer is a Wilms'"'"' tumor, an acute myelogenous leukemia (AML), a myelodysplastic syndrome (MDS), a mesothelioma or a non-small cell lung cancer (NSCLC).

14. A pharmaceutical composition comprising the expression vector of claim 2.

15. The expression vector of claim 2, wherein the vector is an attenuated viral vector or a Salmonella typhi vector.

16. The expression vector of claim 2, further encoding an immunomodulatory compound.

17. The expression vector of claim 16, wherein the immunomodulatory compound is a cytokine, chemokine, or complement component that enhances expression of immune system accessory or adhesion molecules, their receptors, or a combination thereof.

18. The expression vector of claim 16, wherein the immunomodulatory compound is any of interleukins 1 to 15 interferons alpha, beta or gamma, tumour necrosis factor, granulocyte-macrophage colony stimulating factor (GM-CSF), macrophage colony stimulating factor (M-CSF), granulocyte colony stimulating factor (G-CSF), a chemokine such as neutrophil activating protein (NAP), macrophage chemoattractant and activating factor (MCAF), RANTES, or macrophage inflammatory peptides MIP-1a or MIP-1b.

19. A vaccine comprising the nucleic acid expression vector of claim 2.

20. The vaccine of claim 19 further comprising an adjuvant, carrier or antigen presenting cell.

21. The vaccine of claim 20 wherein the adjuvant is QS21, Freund'"'"'s incomplete adjuvant, aluminum phosphate, aluminum hydroxide, BCG, alum, a growth factor, a cytokine, a chemokine, an interleukin, Montanide ISA 51, or GM-CSF.