WT1 HLA CLASS II-BINDING PEPTIDES AND COMPOSITIONS AND METHODS COMPRISING SAME

• US 20190322713A1
• Filed: 02/07/2019
• Published: 10/24/2019
• 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, Pinilla-Ibarz, Javier, May, Rena
• Granted Patent: US 11,548,924 B2
• Time in Patent Office: Days
• CPC Class Codes: A61K 2039/5158 Antigen-pulsed cells, e.g. T-cells
• 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 composition comprising an isolated WT1 peptide having the amino acid sequence RSDELVRHHNMHQRNMTKL (SEQ ID No:

2), PGCNKRYFKLSHLQMHSRKHTG (SEQ ID No;

     4) or the combination thereof, and a diluent.

10. The composition of claim 1 further comprising an immunomodulating compound.

13. The composition of claim 1 comprising the peptide PGCNKRYFKLSHLQMHSRKHTG (SEQ ID No:

4) and the peptide RSDELVRHHNMHQRNMTKL (SEQ ID No;

     2).

14. The composition of claim 13 further comprising YMFPNAPYL (SEQ ID NO:

6).

26. A method of treating a subject with a WT1-expressing cancer, reducing an incidence of a WT1-expressing cancer, or its relapse, the method comprising administering to said subject the composition of claim 1, thereby treating a subject with a WT1-expressing cancer, reducing an incidence of a WT1-expressing cancer, or its relapse.

27. The method of claim 26, 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, a mesothelioma, or a hepatocellular carcinoma.

28. The method of claim 26, wherein said WT1-expressing cancer is a Wilms'"'"' tumor, an acute myelogenous leukemia (AML), a myelodysplastic syndrome (MDS), or a non-small cell lung cancer (NSCLC).

32. 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 composition of claim 1, thereby inducing the formation and proliferation of CTL specific for cells of a WT1-expressing cancer.

33. The method of claim 32, 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, a mesothelioma, or a hepatocellular carcinoma.

34. The method of claim 32, wherein said WT1-expressing cancer is a Wilms'"'"' tumor, an acute myelogenous leukemia (AML), a myelodysplastic syndrome (MDS), or a non-small cell lung cancer (NSCLC).

65. The composition of claim 10 wherein the immunomodulating compound is a cytokine, chemokine, or complement component that enhances expression of immune system accessory or adhesion molecules, their receptors, or combinations thereof. In some embodiments.

66. The composition of claim 10 wherein the immunomodulating compound an interleukin, for example 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, macrophage inflammatory peptides MIP-1a and MIP-1b, complement components, or combinations thereof.

67. The composition of claim 10 wherein the immunomodulating compound stimulates expression, or enhances expression of OX40, OX40L (gp34), lymphotactin, CD40, CD40L, B7.1, B7.2, TRAP, ICAM-1, 2 or 3, cytokine receptors, CD40 or its ligand, CD28, CTLA-4, a B7 molecule, a heat stable antigen (HSA), chondroitin sulfate-modified MHC invariant chain (Ii-CS), or an intracellular adhesion molecule 1 (ICAM-1), or combinations thereof.

2-9. -9. (canceled)

11. (canceled)

15-25. -25. (canceled)

29-31. -31. (canceled)

35-60. -60. (canceled)

61. A method of inducing an anti-mesothelioma immune response in a subject, treating a subject with mesothelioma, or reducing the incidence or relapse of mesothelioma, the method comprising the step of contacting said subject with an immunogenic composition or vaccine comprising a peptide having the amino acid sequence RSDELVRHHNMHQRNMTKL (SEQ ID No:

2), a peptide having the amino acid sequence PGCNKRYFKLSHLQMHSRKHTG (SEQ ID No;

     4) or the combination thereof, thereby inducing an anti-mesothelioma immune response, treating the mesothelioma, or reducing the incidence or relapse of mesothelioma in the subject.

64. The method of claim 61 wherein the immunogenic composition comprises an adjuvant, a carrier, a diluent or an antigen presenting cell.

62-63. -63. (canceled)

68. A composition comprising an isolated WT1 peptide having the amino acid sequence RSDELVRHHNMHQRNMTKL (SEQ ID No:

2), PGCNKRYFKLSHLQMHSRKHTG (SEQ ID No;

     4) or the combination thereof, and an immunomodulating compound.

69. The composition of claim 68 wherein the immunomodulating compound is a cytokine, chemokine, or complement component that enhances expression of immune system accessory or adhesion molecules, their receptors, or combinations thereof. In some embodiments.

70. The composition of claim 68 wherein the immunomodulating compound an interleukin, for example 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, macrophage inflammatory peptides MIP-1a and MIP-1b, complement components, or combinations thereof.

71. The composition of claim 68 wherein the immunomodulating compound stimulates expression, or enhances expression of OX40, OX40L (gp34), lymphotactin, CD40, CD40L, B7.1, B7.2, TRAP, ICAM-1, 2 or 3, cytokine receptors, CD40 or its ligand, CD28, CTLA-4, a B7 molecule, a heat stable antigen (HSA), chondroitin sulfate-modified MHC invariant chain (Ii-CS), or an intracellular adhesion molecule 1 (ICAM-1), or combinations thereof.