Combination Treatment

Abstract

Human clinical use of a chimeric poliovirus construct has demonstrated excellent anti-tumor effect. Combination with immune checkpoint inhibitors increases the anti-tumor effect. Tumors of different types are susceptible to the combination treatment, including but not limited to melanoma, glioglastoma, renal cell carcinoma, prostate cancer, breast cancer, lung cancer, medulloblastoma, and colorectal cancer.

We claim: 
     
         1 . A method of treating a tumor in a patient, comprising:
 administering to the patient a PVSRIPO chimeric poliovirus construct comprising a Sabin type I strain of poliovirus with a human rhinovirus 2 (HRV2) internal ribosome entry site (IRES) in said poliovirus' 5′ untranslated region between said poliovirus' cloverleaf and said poliovirus' open reading frame; and   administering an anti-PD-1 antibody, whereby the patient is treated.   
     
     
         2 . A method of treating a tumor in a patient, comprising:
 administering to the patient a PVSRIPO chimeric poliovirus construct comprising a Sabin type I strain of poliovirus with a human rhinovirus 2 (HRV2) internal ribosome entry site (IRES) in said poliovirus' 5′ untranslated region between said poliovirus' cloverleaf and said poliovirus' open reading frame; and   administering an anti-PD-L1 antibody to the patient, whereby the patient is treated.   
     
     
         3 . The method of  claim 1  or  2  wherein the tumor is a glioblastoma. 
     
     
         4 . The method of  claim 1  or  2  wherein the tumor is astrocytoma or oligodendroglioma. 
     
     
         5 . The method of  claim 1  or  2  wherein the tumor is astro-oligodendroglioma. 
     
     
         6 . The method of  claim 1  or  2  wherein the tumor is renal cell carcinoma. 
     
     
         7 . The method of  claim 1  or  2  wherein the tumor is prostate tumor. 
     
     
         8 . The method of  claim 1  or  2  wherein the tumor is bladder tumor. 
     
     
         9 . The method of  claim 1  or  2  wherein the tumor is esophagus and/or stomach tumor. 
     
     
         10 . The method of  claim 1  or  2  wherein the tumor is pancreas tumor. 
     
     
         11 . The method of  claim 1  or  2  wherein the tumor is colorectal tumor. 
     
     
         12 . The method of  claim 1  or  2  wherein the tumor is liver or gall bladder tumor. 
     
     
         13 . The method of  claim 1  or  2  wherein the tumor is breast tumor. 
     
     
         14 . The method of  claim 1  or  2  wherein the tumor is medulloblastoma. 
     
     
         15 . The method of  claim 1  or  2  wherein the tumor is lung tumor. 
     
     
         16 . The method of  claim 1  or  2  wherein the tumor is head and neck tumor. 
     
     
         17 . The method of  claim 1  or  2  wherein the tumor is melanoma. 
     
     
         18 . The method of  claim 1  or  2  wherein the tumor is sarcoma. 
     
     
         19 . The method of  claim 1  or  2  wherein the chimeric poliovirus construct is administered by intracerebral infusion with convection enhanced delivery. 
     
     
         20 . The method of  claim 1  or  2  wherein prior to administering, the method comprises the step of testing the tumor to ascertain that it expresses NECL5. 
     
     
         21 . The method of  claim 1  or  2  wherein the tumor expresses NECL5. 
     
     
         22 . The method of  claim 1  or  2  wherein the chimeric poliovirus construct is administered directly to the tumor. 
     
     
         23 . The method of  claim 1  or  2  wherein the antibody is administered within 30 days of administering the chimeric poliovirus construct. 
     
     
         24 . The method of  claim 1  or  2  wherein the antibody is administered within 7 days of administering the chimeric poliovirus construct. 
     
     
         25 . The method of  claim 1  or  claim 2 , wherein administration of the antibody is repeated. 
     
     
         26 . The method of  claim 1  wherein the antibody is pembrolizumab. 
     
     
         27 . The method of  claim 1  wherein the antibody is nivolumab. 
     
     
         28 . A kit in a divided container for treating a tumor that expresses NECL5 (nectin-like protein 5), comprising:
 a PVSRIPO chimeric poliovirus construct comprising a Sabin type I strain of poliovirus with a human rhinovirus 2 (HRV2) internal ribosome entry site (IRES) in said poliovirus' 5′ untranslated region between said poliovirus' cloverleaf and said poliovirus' open reading frame; and   an anti-PD-1 antibody, wherein the chimeric poliovirus construct and the antibody are in distinct vessels of the divided container.   
     
     
         29 . The kit of  claim 28  wherein the antibody is pembrolizumab. 
     
     
         30 . The kit of  claim 28  wherein the antibody is nivolumab. 
     
     
         31 . A kit in a divided container for treating a tumor that expresses NECL5 (nectin-like protein 5), comprising:
 a PVSRIPO chimeric poliovirus construct which comprises a Sabin type I strain of poliovirus with a human rhinovirus 2 (HRV2) internal ribosome entry site (IRES) in said poliovirus' 5′ untranslated region between said poliovirus' cloverleaf and said poliovirus' open reading frame; and   an anti-PD-L1 antibody, wherein the chimeric poliovirus construct and the antibody are in distinct vessels of the divided container.   
     
     
         32 . A composition comprising a PVSRIPO chimeric poliovirus construct and an anti-PD-1 antibody; wherein the chimeric poliovirus construct comprises a Sabin type I strain of poliovirus with a human rhinovirus 2 (HRV2) internal ribosome entry site (IRES) in said poliovirus' 5′ untranslated region between said poliovirus' cloverleaf and said poliovirus' open reading frame. 
     
     
         33 . The composition of  claim 32  wherein the antibody is pembrolizumab. 
     
     
         34 . The composition of  claim 32  wherein the antibody is nivolumab. 
     
     
         35 . A composition comprising a PVSRIPO chimeric poliovirus construct and an anti-PD-L1 antibody; wherein the chimeric poliovirus construct comprises a Sabin type I strain of poliovirus with a human rhinovirus 2 (HRV2) internal ribosome entry site (IRES) in said poliovirus' 5′ untranslated region between said poliovirus' cloverleaf and said poliovirus' open reading frame.