Immune effector cells pre-infected with oncolytic virus

Abstract

Compositions and methods are provided for the treatment of cancer. An immune effector cell population is pre-infected with an oncolytic virus. The combined therapeutic is safe and highly effective, producing an enhanced anti-tumor effect compared to either therapy alone. The methods of the invention thus provide for a synergistic effect based on the combined biotherapeutics.

1 - 19 . (canceled) 
     
     
         20 . An isolated mammalian immune effector cell population, infected with an oncolytic virus, wherein the oncolytic virus has a prolonged eclipse period in the immune effector cell population and wherein the oncolytic virus is a reovirus, a herpes simplex virus 1 (HSV-1), or a vesicular stomatitis virus (VSV). 
     
     
         21 . The cell population of  claim 20 , wherein the prolonged eclipse period of the oncolytic virus is from about 1 day to about 4 days. 
     
     
         22 . The cell population of  claim 20 , wherein the oncolytic virus is genetically modified to reduce replication in non-transformed cells but not tumor cells. 
     
     
         23 . The cell population of  claim 20 , wherein the oncolytic virus is an HSV-1 comprising a deletion of a ribonucleotide reductase subunit gene or thymidine kinase (TK) gene. 
     
     
         24 . The cell population of  claim 20 , wherein said cell population is human. 
     
     
         25 . The cell population of  claim 20 , wherein the immune effector cell is a T cell. 
     
     
         26 . The cell population of  claim 25 , wherein the T cell is a tumor-infiltrating T cell or a cytotoxic T lymphocyte (CTL). 
     
     
         27 . The cell population of  claim 20 , wherein the immune effector cell is an NK cell. 
     
     
         28 . The cell population of  claim 27 , wherein the NK cell is a lymphokine-activated killer (LAK) cell or a cytotoxic induced killer (CIK) cell. 
     
     
         29 . The cell population of  claim 20 , wherein said effector cell is a CD56+ effector cell. 
     
     
         30 . The cell population of  claim 20 , wherein said effector cell is a CD3+ CD56+ effector cell. 
     
     
         31 . The cell population of  claim 20 , wherein said immune effector cells are expanded in in vitro culture. 
     
     
         32 . The cell population of  claim 20 , wherein said replication of said oncolytic virus is in an eclipse phase. 
     
     
         33 . The cell population of  claim 20 , further comprising a pharmaceutically acceptable excipient. 
     
     
         34 . A method of treating cancer in a patient, the method comprising:
 administering to a cancer patient an effective amount of a mammalian immune effector cell population infected with an oncolytic virus, wherein the oncolytic virus is a reovirus, a herpes simplex virus 1 (HSV-1), or a vesicular stomatitis virus (VSV).   
     
     
         35 . The method of  claim 34 , wherein the prolonged eclipse period of the oncolytic virus is from about 1 day to about 4 days. 
     
     
         36 . The method of  claim 34 , wherein the oncolytic virus is genetically modified to reduce replication in non-transformed cells but not tumor cells. 
     
     
         37 . The method of  claim 34 , wherein the oncolytic virus is an HSV-1 comprising a deletion of a ribonucleotide reductase subunit gene or thymidine kinase (TK) gene. 
     
     
         38 . The cell population according to  claim 34 , wherein said cell population is human. 
     
     
         39 . The method of  claim 34 , wherein the immune effector cell is a T cell. 
     
     
         40 . The cell population according to  claim 25 , wherein the T cell is a tumor-infiltrating T cell or a cytotoxic T lymphocyte (CTL). 
     
     
         41 . The method of  claim 34 , wherein the immune effector cell is an NK cell. 
     
     
         42 . The cell population according to  claim 27 , wherein the NK cell is a lymphokine-activated killer (LAK) cell or a cytotoxic induced killer (CIK) cell. 
     
     
         43 . The method of  claim 34 , wherein said effector cell is a CD56+θeffector cell. 
     
     
         44 . The method of  claim 34 , wherein said effector cell is a CD3+ CD56+ effector cell. 
     
     
         45 . The method of  claim 34 , wherein said immune effector cells are expanded in in vitro culture. 
     
     
         46 . The method of  claim 34 , wherein said replication of said oncolytic virus is in an eclipse phase. 
     
     
         47 . The method according to  claim 34 , wherein the immune effector cells are autologous cells. 
     
     
         48 . The method according to  claim 34 , wherein the immune effector cells are allogeneic cells.