Combination method for treatment of cancer

Abstract

The invention relates to methods of treating tumours comprising delivering an oncolytic virus or oncolytic viral RNA via direct injection or systemic administration or intravesicular administration to the tumour or cancer in combination with the co-administration of an immuno-stimulatory agent via the systemic route to a mammal.

1 . A method for the treatment of cancer in a subject, the method comprising delivering an oncolytic virus or oncolytic viral RNA via direct injection to a tumor or systemic administration to the subject in combination with the co-administration of an immuno-stimulatory agent via the systemic route to the subject. 
     
     
         2 . A method for the treatment of bladder cancer in a subject, the method comprising delivering an oncolytic virus or oncolytic viral RNA via direct injection to a tumor or systemic administration or intravesicular administration to the subject in combination with the co-administration of an immuno-stimulatory agent via the systemic route to the subject. 
     
     
         3 . The method of  claim 1  or  2 , wherein the oncolytic virus or oncolytic viral RNA is selected from the group consisting of Family Picomaviridae. 
     
     
         4 . The method of  claim 1  or  2 , wherein the oncolytic virus or oncolytic viral RNA selected from the group consisting of Family Picomaviridae virus that bind to intercellular adhesion molecule-1 (ICAM-1) and/or decay-accelerating factor (DAF) on the surface of the tumour cell. 
     
     
         5 . The method of  claim 1  or  2 , wherein the oncolytic virus or oncolytic viral RNA is selected from the group consisting of genus enterovirus that bind to intercellular adhesion molecule-1 (ICAM-1) and/or decay-accelerating factor (DAF) on the surface of the tumour cell. 
     
     
         6 . The method of  claim 1  or  2 , wherein the oncolytic virus or oncolytic viral RNA is selected from the group consisting of Group A Coxsackievirus that bind to intercellular adhesion molecule-1 (ICAM-1) and/or decay-accelerating factor (DAF) on the surface of the tumour cell. 
     
     
         7 . The method of  claim 1  or  2 , wherein the oncolytic virus or oncolytic viral RNA is Coxsackievirus A21. 
     
     
         8 . The method of  claim 1  or  2 , wherein the immunostimulatory agent is selected from the group consisting of a agent that specifically binds to the surface expressed PD-1, PD-L1, PD-L2, CTLA-4 or OX-40. 
     
     
         9 . The method of  claim 1  or  2 , wherein the immunostimulatory agent is selected from the group consisting of a monoclonal antibody that specifically binds to the surface expressed PD-1, PD-L1, PD-L2, CTLA-4 or OX-40. 
     
     
         10 . The method of  claim 1  or  2 , wherein delivering the oncolytic virus or oncolytic viral RNA via direct injection or systemic administration or intravesicular administration is prior to the administration of an immuno-stimulatory agent via the systemic route. 
     
     
         11 . The method of  claim 1  or  2 , wherein delivering the oncolytic virus or oncolytic viral RNA via direct injection or systemic administration or intravesicular administration is following the administration of an immuno-stimulatory agent via the systemic route to the subject. 
     
     
         12 . The method of  claim 1  or  2 , wherein the cancer or tumour is selected from the group consisting of prostate cancer, breast cancer, ovarian cancer, lymphoid cancer, leukemia, brain cancer, lung cancer, colorectal cancer, thyroid cancer, renal cancer, adrenal cancer, liver cancer, stomach cancer, intestinal cancer, bladder cancer, cancer of the kidney, multiple myeloma, non-small cell lung cancer (NSCLC), pancreatic cancer, glioblastoma and melanoma. 
     
     
         13 . The method of  claim 1  or  2 , wherein the cancer or tumour is melanoma. 
     
     
         14 . Use of oncolytic virus or oncolytic viral RNA for the manufacture of a medicament for the treatment of a subject having cancer, wherein said medicament is for use in combination with an immuno-stimulatory agent delivered via the systemic route to the subject, and wherein said medicament is for delivery via direct injection to the tumor or systemic administration to the subject. 
     
     
         15 . Use of oncolytic virus or oncolytic viral RNA for the manufacture of a medicament for the treatment of a subject having bladder cancer, wherein said medicament is for use in combination with an immuno-stimulatory agent delivered via the systemic route to the subject, and wherein said medicament is for delivery via direct injection to a tumor or systemic administration or intravesicular administration to the subject. 
     
     
         16 . The use according to  claim 14  or  15 , wherein the oncolytic virus or oncolytic viral RNA is for administration to the subject via direct injection to a tumour or systemic administration or intravesicular administration to the subject prior to the administration of an immuno-stimulatory agent via the systemic route to the mammal. 
     
     
         17 . The use according to  claim 14  or  15 , wherein the medicament comprising an oncolytic virus or oncolytic viral RNA is for administration to the subject via direct injection to a tumor or systemic administration or intravesicular administration to the subject following the administration of an immuno-stimulatory agent via the systemic route to the subject. 
     
     
         18 . An oncolytic virus or oncolytic viral RNA for use in treatment of a subject having cancer, wherein said use is in combination with an immuno-stimulatory agent, wherein in said use the oncolytic virus or oncolytic viral RNA is administered to said subject via direct injection to a tumor or systemic administration to the subject and said immuno-stimulatory agent is administered via the systemic route to the subject. 
     
     
         19 . An oncolytic virus or oncolytic viral RNA for use in treatment of a subject having bladder cancer, wherein said use is in combination with an immuno-stimulatory agent, wherein in said use the oncolytic virus or oncolytic viral RNA is administered to said subject via direct injection to a tumor or systemic administration or intravesicular administration to the subject and said immuno-stimulatory agent is administered via the systemic route to the subject. 
     
     
         20 . The oncolytic virus or oncolytic viral RNA for use according to  claim 18  or  19 , wherein the administration of said oncolytic virus or oncolytic viral RNA is prior to the administration of the immuno-stimulatory agent. 
     
     
         21 . The oncolytic virus or oncolytic viral RNA for use according to  claim 18  or  19 , wherein the administration of said oncolytic virus or oncolytic viral RNA is after the administration of the immuno-stimulatory agent. 
     
     
         22 . The method according to  claim 1  or  2 , wherein the subject is a human.