Rna viruses for immunovirotherapy

Abstract

The present invention relates to a recombinant virus of the family Paramyxoviridae, comprising at least one expressible polynucleotide encoding a multispecific binding polypeptide, said multispecific binding polypeptide comprising a first binding domain binding to a surface molecule of an immune cell with antitumor activity, preferably a lymphocyte, more preferably a T cell or a dendritic cell, and a second binding domain binding to a tumor-associated antigen; to a polynucleotide encoding the same, and to a kit comprising the same. Moreover, the present invention relates to a method for treating cancer in a subject afflicted with cancer, comprising contacting said subject with a recombinant virus of the family Paramyxoviridae of the invention, and thereby, treating cancer in a subject afflicted with cancer.

What is claimed is: 
     
         1 . A recombinant virus of the family Paramyxoviridae, comprising at least one expressible polynucleotide encoding a multispecific binding polypeptide, said multispecific binding polypeptide comprising:
 a) a first binding domain binding to a surface molecule of an immune cell with antitumor activity, wherein said immune cell is a T cell, and wherein said surface molecule is CD3, and   b) a second binding domain binding to a tumor-associated antigen.   
     
     
         2 . The recombinant virus of the family Paramyxoviridae of  claim 1 , wherein said tumor-associated antigen is selected from the group consisting of androgen receptor (AR), BCL-1, calprotectin, carcinoembryonic antigen (CEA), EGFRs, epithelial cell adhesion molecule (Ep-CAM), epithelial sialomucin, membrane estrogen receptors (mER), FAP, HER2/neu, human high molecular weight melanoma-associated antigen (HMW-MAA), IL-6, MOC-1, MOC-21, MOC-52, melan-A/MART-1, melanoma-associated antigen, mucin, OKT9, progesterone receptor (PGR), prostate specific antigen (PSA), prostate stem cell antigen (PSCA), prostate-specific membrane antigen (PSMA), symaptophysin, VEGFRs, CD19, CD20, CD22, CD30 and CD33. 
     
     
         3 . The recombinant virus of the family Paramyxoviridae of  claim 1 , wherein said tumor-associated antigen is CEA or CD20 
     
     
         4 . The recombinant virus of the family Paramyxoviridae of  claim 1 , wherein said multispecific binding polypeptide is a bispecific binding polypeptide. 
     
     
         5 . The recombinant virus of the family Paramyxoviridae of  claim 1 , wherein said recombinant virus is a recombinant Morbillivirus. 
     
     
         6 . The recombinant virus of the family Paramyxoviridae of  claim 1 , wherein said recombinant virus is a recombinant measles virus (MV). 
     
     
         7 . The recombinant virus of the family Paramyxoviridae of  claim 1 , wherein said first binding domain comprises a single-chain antibody against CD3. 
     
     
         8 . The recombinant virus of the family Paramyxoviridae of  claim 1 , wherein said second binding domain comprises a single-chain antibody against CEA. 
     
     
         9 . The recombinant virus of the family Paramyxoviridae of  claim 1 , wherein said second binding domain comprises a single-chain antibody against CD20. 
     
     
         10 . The recombinant virus of the family Paramyxoviridae of  claim 1 , wherein the at least one expressible polynucleotide encoding a multispecific binding polypeptide is comprised in a polynucleotide encoding the recombinant virus of the family Paramyxoviridae. 
     
     
         11 . The recombinant virus of the family Paramyxoviridae of  claim 1 , wherein said multispecific binding polypeptide further comprises a cytokine. 
     
     
         12 . A polynucleotide encoding the recombinant virus of the family Paramyxoviridae according to  claim 1 . 
     
     
         13 . A combined preparation for simultaneous, separate or sequential use comprising at least one virus of the family Paramyxoviridae and at least one multispecific binding polypeptide. 
     
     
         14 . An in vitro method for treating activating immune cells with antitumor activity in a sample comprising cancer cells and immune cells, comprising
 a) contacting said sample comprising cancer cells and immune cells with a recombinant virus of the family Paramyxoviridae of  claim 1 , and   b) thereby, activating immune cells with antitumor activity comprised in said sample.   
     
     
         15 . A method for treating cancer in a subject afflicted with cancer, comprising
 a) contacting said subject with a recombinant virus of the family Paramyxoviridae according to  claim 1 , and   b) thereby, treating cancer in a subject afflicted with cancer.   
     
     
         16 . The method of  claim 15 , wherein step a further comprises contacting said subject with a multispecific binding polypeptide. 
     
     
         17 . A kit comprising at least the recombinant virus of the family Paramyxoviridae according to  claim 1  housed in a container.