Therapeutic methods and compositions using viruses of the recombinant paramyxoviridae family

Abstract

The invention relates to compositions and methods for treating a patient having a tumor in order to reduce tumor size, comprising administering to the patient a replication-competent Paramyxoviridae virus comprising two or more of a) a nucleic acid sequence encoding a heterologous polypeptide, wherein upon administration the heterologous polypeptide is detectable in a biological fluid of the patient, and detection of the heterologous polypeptide is indicative of Paramyxoviridae virus growth in the patient and reduction in tumor size; b) a recombinant F protein, H protein, or M protein of Paramyxoviridae virus that increases fusogenicity of virus with cells; c) a nucleic acid sequence encoding a cytokine; and d) a Paramyxoviridae virus that is specific for cells of the tumor.

1 - 26 . (canceled)  
     
     
         27 . A method for delivering a Paramyxoviridae virus to a tumor in a mammal, said method comprises administering said Paramyxoviridae virus to said mammal under conditions wherein said Paramyxoviridae virus enters a cell in said tumor, wherein said Paramyxoviridae virus comprises a polypeptide comprising a Paramyxoviridae virus polypeptide sequence and a heterologous sequence, wherein said heterologous sequence binds to a receptor present on said cell.  
     
     
         28 . The method of  claim 27 , wherein said Paramyxoviridae virus is a measles virus.  
     
     
         29 . The method of  claim 27 , wherein said heterologous sequence is fused via an intervening amino acid linker to said Paramyxoviridae virus polypeptide sequence.  
     
     
         30 . The method of  claim 27 , wherein said Paramyxoviridae virus polypeptide sequence comprises an amino acid sequence of a Paramyxoviridae virus F or H protein.  
     
     
         31 . The method of  claim 27 , wherein said heterologous sequence is a single chain antibody.  
     
     
         32 . The method of  claim 31 , wherein said single chain antibody binds a carcinoembryonic antigen.  
     
     
         33 . The method of  claim 31 , wherein said single chain antibody binds a CD38 polypeptide.  
     
     
         34 . The method of  claim 27 , wherein said heterologous sequence is an EGF polypeptide.  
     
     
         35 . The method of  claim 27 , wherein said heterologous sequence is an IGF-1 polypeptide.  
     
     
         36 . The method of  claim 27 , wherein said receptor is a carcinoembryonic antigen, a CD38 polypeptide, an EGF receptor polypeptide, or an IGF-1 receptor polypeptide.  
     
     
         37 . A Paramyxoviridae virus comprising a polypeptide comprising a Paramyxoviridae virus polypeptide sequence and a heterologous sequence, wherein said heterologous sequence binds to a receptor present on a cell in a tumor.  
     
     
         38 . The Paramyxoviridae virus of  claim 27 , wherein said Paramyxoviridae virus is a measles virus.  
     
     
         39 . The Paramyxoviridae virus of  claim 27 , wherein said heterologous sequence is fused via an intervening amino acid linker to said Paramyxoviridae virus polypeptide sequence.  
     
     
         40 . The Paramyxoviridae virus of  claim 27 , wherein said Paramyxoviridae virus polypeptide sequence comprises an amino acid sequence of a Paramyxoviridae virus F or H protein.  
     
     
         41 . The Paramyxoviridae virus of  claim 27 , wherein said heterologous sequence is a single chain antibody.  
     
     
         42 . The Paramyxoviridae virus of  claim 41 , wherein said single chain antibody binds a carcinoembryonic antigen.  
     
     
         43 . The Paramyxoviridae virus of  claim 41 , wherein said single chain antibody binds a CD38 polypeptide.  
     
     
         44 . The Paramyxoviridae virus of  claim 27 , wherein said heterologous sequence is an EGF polypeptide.  
     
     
         45 . The Paramyxoviridae virus of  claim 27 , wherein said heterologous sequence is an IGF-1 polypeptide.  
     
     
         46 . The Paramyxoviridae virus of  claim 27 , wherein said receptor is a carcinoembryonic antigen, a CD38 polypeptide, an EGF receptor polypeptide, or an IGF-1 receptor polypeptide.