Use of Oncolytic Herpes Simplex Virus, Alone or in Combination with Immune Check-Point Inhibitor, in the Treatment of Cancer

Abstract

An oncolytic herpes simplex virus is disclosed for use in a method of treating cancer, the method comprising administering one or more doses of an oncolytic herpes simplex virus effective to induce a Th1 immune response in the subject, and optionally administering a therapeutically effective amount of an immune checkpoint inhibitor.

1 .- 35 . (canceled) 
     
     
         36 . A pharmaceutical composition comprising an oncolytic herpes simplex virus and an immune checkpoint inhibitor, wherein the oncolytic herpes simplex virus does not contain a functional γ 1 34.5 gene, encodes a functional ICP47 gene, and does not express GMCSF, and wherein the immune checkpoint inhibitor is an antibody or small molecule inhibitor of at least one of CTLA-4, TIM-3, LAG-3, CD80, CD86, PD-L2, BTLA, KIR, VISTA, A2aR, B7-H3, and B7-H4. 
     
     
         37 . The pharmaceutical composition of  claim 36 , wherein the oncolytic herpes simplex virus is a mutant of HSV-1 strain 17. 
     
     
         38 . The pharmaceutical composition of  claim 37 , wherein the oncolytic herpes simplex virus is HSV-1716 or a mutant thereof. 
     
     
         39 . A kit comprising a predetermined amount of oncolytic herpes simplex virus and a predetermined amount of an immune checkpoint inhibitor, wherein the oncolytic herpes simplex virus does not contain a functional γ 1 34.5 gene, encodes a functional ICP47 gene, and does not express GMCSF, and wherein the immune checkpoint inhibitor is an antibody or small molecule inhibitor of at least one of CTLA-4, TIM-3, LAG-3, CD80, CD86, PD-L2, BTLA, KIR, VISTA, A2aR, B7-H3, and B7-H4. 
     
     
         40 . The kit according to  claim 39 , wherein the oncolytic herpes simplex virus is a mutant of HSV-1 strain 17. 
     
     
         41 . The kit according to  claim 40 , wherein the oncolytic herpes simplex virus is HSV1716 or a mutant thereof. 
     
     
         42 . A product containing therapeutically effective amounts of (i) an oncolytic herpes simplex virus, and (ii) an immune checkpoint inhibitor, wherein the oncolytic herpes simplex virus does not contain a functional γ 1 34.5 gene, encodes a functional ICP47 gene and does not express GMCSF, and wherein the immune checkpoint inhibitor is an antibody or small molecule inhibitor of at least one of CTLA-4, TIM-3, LAG-3, CD80, CD86, PD-L2, BTLA, KIR, VISTA, A2aR, B7-H3, and B7-H4. 
     
     
         43 . The product according to  claim 42 , wherein the oncolytic herpes simplex virus is a mutant of HSV-1 strain 17. 
     
     
         44 . The product according to  claim 43 , wherein the oncolytic herpes simplex virus is HSV1716 or a mutant thereof. 
     
     
         45 . A method of treating cancer in a subject, the method comprising simultaneous or sequential administration of oncolytic herpes simplex virus and an immune checkpoint inhibitor, wherein the oncolytic herpes simplex virus does not contain a functional γ 1 34.5 gene, encodes a functional ICP47 gene, and does not express GMCSF, and wherein the immune checkpoint inhibitor is an antibody or small molecule inhibitor of at least one of CTLA-4, TIM-3, LAG-3, CD80, CD86, PD-L2, BTLA, KIR, VISTA, A2aR, B7-H3, and B7-H4. 
     
     
         46 . The method according to  claim 45 , wherein the oncolytic herpes simplex virus is a mutant of HSV-1 strain 17. 
     
     
         47 . The method according to  claim 46 , wherein the oncolytic herpes simplex virus is HSV1716 or a mutant thereof. 
     
     
         48 . The method according to  claim 45 , wherein the method comprises administering one or more doses of the oncolytic herpes simplex virus effective to induce a Th1 immune response. 
     
     
         49 . The method of  claim 48 , wherein the method further comprises determining the presence of a Th1 immune response in the subject.