Measles virus encoding a tumor antigen

Abstract

The present invention relates to a recombinant virus of the family Paramyxoviridae comprising an expressible polynucleotide encoding at least one of (i) a tumor antigen, (ii) a fragment of a tumor antigen, and (iii) a variant of (i) or (ii). The present invention further relates to a polynucleotide encoding said recombinant virus of the family Paramyxoviridae and to a host cell comprising said recombinant virus of the family Paramyxoviridae and/or said polynucleotide encoding said recombinant virus of the family Paramyxoviridae. Moreover, the present invention relates to a method for activating immune cells with antitumor activity in a sample comprising cancer cells and to further means, methods, and uses related to the present invention.

1 - 42 . (canceled) 
     
     
         43 . A replication competent recombinant virus of the family Paramyxoviridae comprising an expressible polynucleotide encoding at least one of (a) the tumor antigen L-dopachrome-tautomerase (TRP2), (b) a fragment of the tumor antigen TRP2 comprising at least one antigenic epitope of TRP2, and (c) a variant of (a) or (b), wherein the variant is 90% identical to the sequence of TRP2 depicted in SEQ ID NO: 2. 
     
     
         44 . The recombinant virus of the family Paramyxoviridae of  claim 43 , wherein said fragment of the tumor antigen TRP2 comprising at least one antigenic epitope of TRP2 comprises a sequence of from 7 to 15 contiguous amino acids. 
     
     
         45 . The recombinant virus of the family Paramyxoviridae of  claim 43 , wherein TRP2 is human TRP2. 
     
     
         46 . The recombinant virus of the family Paramyxoviridae of  claim 43 , wherein said recombinant virus is a recombinant Morbillivirus. 
     
     
         47 . The recombinant virus of the family Paramyxoviridae of  claim 46 , wherein said recombinant Morbillivirus is a recombinant measles virus (MV). 
     
     
         48 . The recombinant virus of the family Paramyxoviridae of  claim 43 , further comprising at least one expressible polynucleotide encoding a further activator of the immune response. 
     
     
         49 . The recombinant virus of the family Paramyxoviridae of  claim 48 , wherein said at least one expressible polynucleotide encoding a further activator of the immune response is comprised in a polynucleotide encoding the recombinant virus of the family Paramyxoviridae. 
     
     
         50 . A polynucleotide encoding the replication competent recombinant virus of  claim 43 . 
     
     
         51 . A host cell comprising the replication competent recombinant virus of  claim 43 . 
     
     
         52 . A method for 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
 (i) the replication competent recombinant virus of the family Paramyxoviridae of  claim 43 ; 
 (ii) a polynucleotide encoding the recombinant virus of the family Paramyxoviridae of a)(i); 
 (iii) a host cell comprising the recombinant virus of the family Paramyxoviridae of a)(i); 
 (iv) a host cell comprising the polynucleotide of a)(ii); or 
 (v) any combination of a)(i) to a)(iv); and thereby, 
   b) activating immune cells with antitumor activity comprised in said sample.   
     
     
         53 . A preparation of activated immune cells with antitumor activity obtained or obtainable by the method of  claim 52 . 
     
     
         54 . A method for treating inappropriate cell proliferation comprising administering to a subject in need thereof:
 (i) the replication competent recombinant virus of the family Paramyxoviridae of  claim 43 ;   (ii) a polynucleotide encoding the replication competent recombinant virus of the family Paramyxoviridae of (i);   (iii) a host cell comprising the replication competent recombinant virus of the family Paramyxoviridae of (i);   (iv) a host cell comprising the polynucleotide of (ii); or   (v) any combination of (i) to (iv).   
     
     
         55 . The method of  claim 54 , wherein said inappropriate cell proliferation is cancer. 
     
     
         56 . A kit comprising
 (i) the replication competent recombinant virus of the family Paramyxoviridae of  claim 43 ;   (ii) a polynucleotide encoding the replication competent recombinant virus of the family Paramyxoviridae of (i);   (iii) a host cell comprising the replication competent recombinant virus of the family Paramyxoviridae of (i);   (iv) a host cell comprising the polynucleotide of (ii); or   (v) any combination of (i) to (iv);   housed in a container.   
     
     
         57 . A host cell comprising the polynucleotide according to  claim 51 .