Treatment of cancer by infusion of oncolytic herpes simplex virus to the blood

Abstract

An oncolytic herpes simplex virus is disclosed for use in a method of treating cancer in a human subject, the method comprising administering to the human subject at least one dose of oncolytic herpes simplex virus by infusion to the blood, wherein the oncolytic herpes simplex virus reaches cells of the cancer in which it replicates.

1 . A method of treating mesothelioma, the method comprising administering to a human subject having mesothelioma at least one dose of a pharmaceutical composition comprising an oncolytic herpes simplex virus (oHSV) by infusion to the blood, wherein the oncolytic herpes simplex virus reaches cells of the cancer in which it replicates and the oHSV is a strain 17 oHSV that does not express a functional ICP34.5 gene product. 
     
     
         2 . (canceled) 
     
     
         3 . (canceled) 
     
     
         4 . The method of  claim 1 , wherein the method comprises determining whether oncolytic herpes simplex virus DNA is present in a sample of the subject's blood. 
     
     
         5 . (canceled) 
     
     
         6 . The method of  claim 1 , wherein the method comprises determining whether oncolytic herpes simplex virus is present in a sample of the subject's tumor tissue. 
     
     
         7 . (canceled) 
     
     
         8 . The method of  claim 1 , wherein the oncolytic herpes simplex virus is HSV1716. 
     
     
         9 . The method of  claim 1 , wherein the cancer is a solid tumor, a recurrent or metastatic solid tumor, or a non-CNS solid tumor. 
     
     
         10 . The method of  claim 1 , wherein the dose of oncolytic herpes simplex virus administered is at least 1×10 6  infectious units (iu). 
     
     
         11 . The method of  claim 1 , wherein a dose of oncolytic herpes simplex virus is administered over a period of 3 hours or less. 
     
     
         12 . The method of  claim 1 , wherein the administered oncolytic herpes simplex virus is formulated as about 0.5 ml to about 5 ml of a suspension of virus in about 200 ml to about 300 ml of lactated Ringer's solution. 
     
     
         13 . The method of  claim 1 , wherein the method comprises administering to the human subject at least one treatment cycle of oncolytic herpes simplex virus, wherein a treatment cycle comprises, or consists, of at least two doses of oncolytic herpes simplex virus, each dose administered by infusion to the blood wherein the second and subsequent doses are each administered within about 17 days of the preceding dose, each dose of oncolytic herpes simplex virus being in the range about 1×10 6  iu to about 1×10 8  iu. 
     
     
         14 . The method of  claim 13 , wherein one dose of oncolytic herpes simplex virus is administered per week. 
     
     
         15 . The method of  claim 13 , wherein two doses of oncolytic herpes simplex virus are administered per week. 
     
     
         16 . The method of  claim 13 , wherein each dose of oncolytic herpes simplex virus is in the range about 1×10 7  iu to about 1×10 8  iu. 
     
     
         17 . (canceled) 
     
     
         18 . The method of  claim 13 , wherein the treatment cycle further comprises, or consists, of administration of a therapeutically effective amount of an immune checkpoint inhibitor selected from the group consisting of an inhibitor of PD-1, PD-L1, CTLA4, TIM-3 or LAG-3. 
     
     
         19 . The method of  claim 13 , wherein the subject receives two or more treatment cycles. 
     
     
         20 . (canceled) 
     
     
         21 . (canceled) 
     
     
         22 . A method of treating mesothelioma, the method comprising administering to a human subject having mesothelioma at least one treatment cycle of oncolytic herpes simplex virus (oHSV), wherein a treatment cycle comprises, or consists, of at least two doses of oncolytic herpes simplex virus, each dose administered by infusion to the blood wherein the second and subsequent doses are each administered within about 17 days of the preceding dose, each dose of oncolytic herpes simplex virus being in the range about 1×10 6  iu to about 1×10 8  iu and the oHSV is a strain 17 oHSV that does not express a functional ICP34.5 gene product. 
     
     
         23 - 59 . (canceled) 
     
     
         60 . The method of  claim 1 , wherein the human subject is a child. 
     
     
         61 . The method of  claim 1 , wherein the oncolytic herpes simplex virus does not encode (or is not further modified to contain nucleic acid encoding) a cytokine or chemokine, an interleukin, an interferon, a tumor necrosis factor, a colony stimulating factor, an immune modulator, a member of the CC family, a member of the CXC family or a member of the CXC family. 
     
     
         62 . The method of  claim 1 , wherein the oncolytic herpes simplex virus does not express GMCSF. 
     
     
         63 . The method of  claim 1 , wherein the oncolytic herpes simplex virus encodes a functional ICP47 and/or ICP6 gene. 
     
     
         64 - 72 . (canceled) 
     
     
         73 . The method of  claim 1 , wherein the mesothelioma is malignant pleural mesothelioma.