Oncolytic rhabdovirus

Abstract

Embodiments of the invention include compositions and methods related to non-VSV rhabdoviruses and their use as anti-cancer therapeutics. Such rhabdoviruses possess tumor cell killing properties in vitro and in vivo.

We claim: 
     
         1 . A pharmaceutical composition comprising a pharmaceutically acceptable carrier and an oncolytic recombinant rhabdovirus encoding a G protein from a first rhabdovirus and M, P, N and L proteins from a second rhabdovirus. 
     
     
         2 . The pharmaceutical composition of  claim 1 , wherein the G protein has at least about 85% amino acid sequence identity to an Isfahan virus G protein, a Chandipura virus G protein, a Maraba virus G protein, a Bahia Grande virus G protein, a Klamath virus G protein, or a Farmington virus G protein. 
     
     
         3 . The pharmaceutical composition of  claim 2 , wherein the oncolytic recombinant rhabdovirus encodes a G protein having at least about 85% amino acid sequence identity to an Isfahan virus G protein, a Chandipura virus G protein, a Maraba virus G protein, or a Muir Springs virus G protein. 
     
     
         4 . The pharmaceutical composition of  claim 3 , wherein the oncolytic recombinant rhabdovirus encodes a G protein having at least about 85% amino acid sequence identity to an Isfahan virus G protein, a Maraba virus G protein, or a Muir Springs virus G protein. 
     
     
         5 . The pharmaceutical composition of  claim 4 , wherein the oncolytic recombinant rhabdovirus encodes a G protein having at least about 85% amino acid sequence identity to a Maraba virus G protein. 
     
     
         6 . The pharmaceutical composition of  claim 1 , wherein the oncolytic recombinant rhabdovirus encodes M, P, N and L proteins from vesicular stomatitis virus (VSV). 
     
     
         7 . The pharmaceutical composition of  claim 2 , wherein the oncolytic recombinant rhabdovirus encodes M, P, N and L proteins from vesicular stomatitis virus (VSV). 
     
     
         8 . The pharmaceutical composition of  claim 3 , wherein the oncolytic recombinant rhabdovirus encodes M, P, N and L proteins from vesicular stomatitis virus (VSV). 
     
     
         9 . The pharmaceutical composition of  claim 4 , wherein the oncolytic recombinant rhabdovirus encodes M, P, N, and L proteins from vesicular stomatitis virus (VSV). 
     
     
         10 . The pharmaceutical composition of  claim 5 , wherein the oncolytic recombinant rhabdovirus encodes M, P, N, and L proteins from vesicular stomatitis virus (VSV). 
     
     
         11 . The pharmaceutical composition of  claim 1 , wherein said composition comprises 10 3  to 10 13  plaque forming units (pfu) of the oncolytic recombinant rhabdovirus. 
     
     
         12 . A method for treating cancer in a subject comprising administering to the subject an effective amount of the pharmaceutical composition of  claim 1 . 
     
     
         13 . The method of  claim 12 , wherein the cancer is selected from the group consisting of lung cancer, head and neck cancer, breast cancer, cancer of the central nervous system, pancreatic cancer, prostate cancer, renal cancer, bone cancer, testicular cancer, cervical cancer, ovarian cancer, gastrointestinal cancer, lymphoma, liver cancer, colon cancer, melanoma, and bladder cancer. 
     
     
         14 . The method of  claim 12 , wherein the cancer is metastatic. 
     
     
         15 . The method of  claim 12 , wherein the subject is a human. 
     
     
         16 . The method of  claim 12 , wherein the composition is administered by intraperitoneal, intravascular, intramuscular, intratumoral, subcutaneous or intranasal administration. 
     
     
         17 . The method of  claim 16 , wherein the composition is administered by intratumoral or intravascular administration. 
     
     
         18 . The method of  claim 12 , wherein the composition is administered multiple times. 
     
     
         19 . The method of  claim 12 , further comprising administering an additional anti-cancer therapy selected from the group consisting of chemotherapy, radiotherapy, and immunotherapy. 
     
     
         20 . A method for treating cancer in a subject comprising administering to the subject an effective amount of an oncolytic recombinant rhabdovirus encoding a G protein from a first rhabdovirus and M, P, N and L proteins from a second rhabdovirus. 
     
     
         21 . The method of  claim 20 , wherein the G protein has at least about 85% amino acid sequence identity to an Isfahan virus G protein, a Chandipura virus G protein, a Maraba virus G protein, a Bahia Grande virus G protein, a Klamath virus G protein, or a Farmington virus G protein. 
     
     
         22 . The method of  claim 21 , wherein the oncolytic recombinant rhabdovirus encodes M, P, N and L proteins from vesicular stomatitis virus (VSV). 
     
     
         23 . The method of  claim 22 , wherein the G protein has at least about 85% amino acid sequence identity to a Maraba virus G protein. 
     
     
         24 . The method of  claim 20 , wherein the cancer is selected from the group consisting of lung cancer, head and neck cancer, breast cancer, cancer of the central nervous system, pancreatic cancer, prostate cancer, renal cancer, bone cancer, testicular cancer, cervical cancer, ovarian cancer, gastrointestinal cancer, lymphoma, liver cancer, lung cancer, colon cancer, melanoma, and bladder cancer.