Compositions and methods for therapy with dengue virus

Abstract

Described herein are compositions and methods for treating a disease, particularly a cancer, with a Dengue Virus and, optionally, primed dendritic cells recognizing a tumor antigen. Lysis protocols are described where the lysis does not result in complete or less than complete lysis of cells in order to provide cell surface molecules maintained in a cell surface-embedded state. Non-lethal Dengue virus strains are also provided for therapeutic purposes.

1 .- 68 . (canceled) 
     
     
         68 . A method of treating or reducing cancer in a subject in need thereof, comprising administering to a subject an effective amount of Dengue virus to treat or reduce a cancer in the subject. 
     
     
         69 . The method of  claim 68 , wherein the Dengue virus is present in an amount of about 10 2  to about 10 8  plaque-forming units (PFU)/mL. 
     
     
         70 . The method of  claim 69 , wherein the Dengue virus is administered at about 10 5  PFU/mL. 
     
     
         71 . The method of  claim 68 , wherein the amount is from about 10,000 PFU/mL to 90,000 PFU/mL. 
     
     
         72 . The method of  claim 68 , wherein the amount is about 30,000 PFU/mL. 
     
     
         73 . The method of  claim 68 , further comprising administering the Dengue virus to the subject in need thereof a second time. 
     
     
         74 . The method of  claim 68 , wherein the cancer is a solid cancer or a hematopoietic cancer. 
     
     
         75 . The method of  claim 74 , wherein the cancer is the solid cancer, and wherein the solid cancer is a bladder cancer, a brain cancer, a breast cancer, a cervical cancer, a gastrointestinal cancer, a kidney cancer, a liver cancer, a lung cancer, an ovarian cancer, a pancreatic cancer, prostate cancer, a sarcoma, a skin cancer, or a uterine cancer. 
     
     
         76 . The method of  claim 75 , wherein the solid cancer is a melanoma. 
     
     
         77 . The method of  claim 76 , wherein the melanoma is V600E positive. 
     
     
         78 . The method of  claim 68 , wherein the cancer is a refractory cancer. 
     
     
         79 . The method of  claim 68 , wherein the Dengue virus is of serotype 1, 2, 3, 4, or 5. 
     
     
         80 . The method of  claim 68 , wherein the Dengue virus is DENV-2 strain #1710. 
     
     
         81 . The method of  claim 68 , wherein the Dengue virus strain is 45AZ5, 1710, S16803, HON 1991 C, HON 1991 D, HON 1991 B, HON 1991 A, SAL 1987, TRI 1981, PR 1969, IND 1957, TM 1953, TSV01, DS09-280106, DS31-291005, 1349, GD01/03, 44, 43, China 04, FJ11/99, FJ-10, QHD13CAIQ, CO/BID-V3358, FRUH21/1971, GU/BID-V2950, American Asian, GWL18, IN/BID-V2961, Od2112, RR44, 1392, 1016DN, 1017DN, 1070DN, 98900663DHF, BA05i, 1022DN, NGC, Pak-L-2011, Pak-K-2009, Pak-M-2011, PakL-2013, Pak-L-2011, Pak-L-2010, Pak-L-2008, PE/NFI1159, PE/IQA 2080, SG/D2Y98P-PP1, SG/05K3295DK1, LK/BID/V2421, LK/BID-V2422, LK/BID-V2416, 1222-DF-06, TW/BID-V5056, TH/BID-V3357, US/BID-V5412, US/BID-V5055, IQT1797, VN/BID-V735, US/Hawaii/1944, CH53489, or 341750. 
     
     
         82 . The method of  claim 68 , wherein the cancer is reduced in size by at least about 60% as measured by computed tomography (CT) scan. 
     
     
         83 . The method of  claim 68 , wherein the cancer is reduced in size by at least about 80% as measured by computed tomography (CT) scan. 
     
     
         84 . The method of  claim 68 , wherein the cancer is reduced in size by at least about 90% as measured by computed tomography (CT) scan. 
     
     
         85 . The method of  claim 68 , wherein the Dengue virus is in a volume of about 0.01 ml, 0.02 ml, 0.03 ml, 0.04 ml, 0.05 ml, or 0.1 ml. 
     
     
         86 . The method of  claim 68 , wherein the Dengue virus is in a volume of about 0.01 ml to 0.1 ml. 
     
     
         87 . The method of  claim 68 , wherein the administering of the Dengue virus comprises a subcutaneous injection to the subject. 
     
     
         88 . The method of  claim 68 , wherein the Dengue virus is in a liquid form, lyophilized form or freeze-dried form. 
     
     
         89 . The method of  claim 68 , wherein the Dengue virus is stored in a container. 
     
     
         90 . The method of  claim 89 , wherein the container is a syringe, vial, bottle, flask, or bag. 
     
     
         91 .- 137 . (canceled)