PDE5 inhibitor compositions and methods for immunotherapy

Patent metadata

Field	Value
Publication number	US-9468643-B2
Application number	US-201414281363-A
Country	US
Kind code	B2
Filing date	May 19, 2014
Priority date	Jan 7, 2005
Publication date	Oct 18, 2016
Grant date	Oct 18, 2016

Abstract

The invention features methods and compositions featuring a PDE5 inhibitor for treating or preventing immunological-mediated disease in a subject.

First claim

What is claimed is:

1. A method of treating cancer in a human patient having myeloid suppressor cell mediated immunosuppression, comprising:
administering adoptive cell transfer therapy comprising lymphocytes to the patient; and
administering a therapeutically effective amount of a phosphodiesterase-5 inhibitor compound to the patient.

2. The method of claim 1 , wherein the patient comprises tumor-infiltrating myeloid suppressor cells.

3. The method of claim 1 , wherein the phosphodiesterase-5 inhibitor compound is sildenafil, vardenafil, or tadalafil.

4. The method of claim 1 , wherein the phosphodiesterase-5 inhibitor compound is administered daily.

5. The method of claim 1 , wherein the cancer is multiple myeloma, a lymphoma, melanoma, breast, stomach, head and neck, ovarian, colon, prostate, lung, or cervical cancer.

6. The method of claim 5 , wherein the cancer is multiple myeloma or head and neck cancer.

7. The method of claim 5 , wherein the cancer is colon cancer.

8. The method of claim 1 , wherein the lymphocytes are tumor infiltrating lymphocytes.

9. A method of treating cancer in a human patient, comprising administering to the patient a therapeutically effective amount of a phosphodiesterase-5 inhibitor compound daily, wherein:
the patient comprises myeloid suppressor cells;
the myeloid suppressor cells are responsible for immune suppression in the patient;
the immune suppression is associated with the cancer; and
the phosphodiesterase-5 inhibitor compound is sildenafil, vardenafil, or tadalafil.

10. The method of claim 9 , further comprising administering an anticancer agent to the patient, wherein the anticancer agent is anthracycline, taxane, an alkylating agent, cis-platin, arabinofuranosyl cytosine, 5-fluorouracil, altretamine, busulfan, chlorambucil, cyclophosphamide, ifosfamide, mechlorethamine, melphalan, thiotepa, cladribine, floxuridine, gemcitabine, thioguanine, pentostatin, methotrexate, 6-mercaptopurine, cytarabine, carmustine, lomustine, streptozotocin, carboplatin, oxaliplatin, iproplatin, tetraplatin, lobaplatin, JM216, JM335, fludarabine, aminoglutethimide, flutamide, goserelin, leuprolide, megestrol acetate, cyproterone acetate, tamoxifen, anastrozole, bicalutamide, dexamethasone, diethylstilbestrol, prednisone, bleomycin, dactinomycin, daunorubicin, doxirubicin, idarubicin, mitoxantrone, losoxantrone, mitomycin-c, plicamycin, paclitaxel, docetaxel, CPI-11, epothilones, topotecan, irinotecan, 9-amino camptothecan, 9-nitro camptothecan, GS-211, etoposide, teniposide, vinblastine, vincristine, vinorelbine, procarbazine, asparaginase, pegaspargase, methoxtrexate, octreotide, estramustine, hydroxyurea, tamoxifen, raloxifene, toremifene, exemestane, letrozole, anastrozole, megestrol, trastuzumab, goserelin acetate, fulvestrant, doxorubicin, epirubicin, or cyclophosphonamide.

11. The method of claim 9 , further comprising administering an anticancer vaccine to the patient, wherein the vaccine is a DNA-based vaccine, a protein-based vaccine, a whole cell tumor vaccine, or a dendritic cell-based vaccine.

12. The method of claim 9 , wherein the myeloid suppressor cells are tumor-infiltrating myeloid suppressor cells.

13. The method of claim 3 , wherein the phosphodiesterase-5 inhibitor compound is tadalafil, and the tadalafil is administered orally at a dose of 5 mg, 10 mg, or 20 mg.

14. The method of claim 13 , wherein the tadalafil is administered orally at a dose of 20 mg.

15. The method of claim 3 , wherein the phosphodiesterase-5 inhibitor compound is vardenafil, and the vardenafil is administered orally at a dose of 5 mg, 10 mg, or 20 mg.

16. The method of claim 3 , wherein the phosphodiesterase-5 inhibitor compound is sildenafil, and the sildenafil is administered orally at a dose of 25 mg, 50 mg, or 100 mg.

Assignees

• Univ Johns Hopkins

Inventors

• Borrello Ivan M
• Serafini Paolo
• Noonan Kimberly A
• Bronte Vincenzo

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61P31/00

  Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics · CPC title

• A61K31/519 Primary

  ortho- or peri-condensed with heterocyclic rings · CPC title

• A61K31/4985

  Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems · CPC title

• A61K31/53 Primary

  having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine (melarsoprol A61K31/555 {; with four nitrogen atoms A61K31/495}) · CPC title