Recombinant virus immunotherapy

Abstract

Attenuated recombinant viruses containing DNA coding for a cytokine and/or a tumor associated antigen, as well as methods and compositions employing the viruses, are disclosed and claimed. The recombinant viruses can be NYVAC or ALVAC recombinant viruses. The DNA can code for at least on of: human tumor necrosis factor; nuclear phosphoprotein p53, wildtype or mutant; human melanoma-associated antigen; IL-2; IFNg; IL-4; GNCSF; IL-12; B7; erb-B-2 and carcinoembryonic antigen. The recombinant viruses and gene products therefrom are useful for cancer therapy.

What is claimed is:  
     
         1 . A method for eliciting an anti-tumor response in a patient having a tumor, wherein the method comprises administering to the patient a recombinant vaccinia virus wherein regions C7L−K1L, J2ER, B13R+B14R, A56R, A26R and I4L have been deleted therefrom; or wherein the open reading frames for the thymidine kinase gene, the hemorrhagic region, the A type inclusion body region, the hemagluttinin gene, the host range gene region, and the gene for the large subunit of ribonucleotide reductase have been deleted therefrom; and wherein the virus further comprises at least one exogenous DNA sequence encoding at least a portion of a tumor antigen expressed by the tumor.  
     
     
         2 . The method of  claim 1  wherein the recombinant vaccinia virus is administered to the patient in admixture with a pharmaceutically suitable carrier.  
     
     
         3 . The method of  claim 1  wherein the tumor antigen is selected from the group consisting of wild-type or mutant p53, carcinoembryonic antigen, and a human melanoma-associated antigen.  
     
     
         4 . The method of  claim 3  wherein the recombinant vaccinia virus is administered to the patient in admixture with a pharmaceutically suitable carrier.  
     
     
         5 . The method of  claim 3  wherein the tumor antigen is wild-type or mutant p53.  
     
     
         6 . The method of  claim 5  wherein the recombinant vaccinia virus is administered to the patient in admixture with a pharmaceutically suitable carrier.  
     
     
         7 . The method of  claim 5  wherein said virus comprises at least one additional exogenous DNA sequence encoding human B7.  
     
     
         8 . The method of  claim 7  wherein the recombinant vaccinia virus is administered to the patient in admixture with a pharmaceutically suitable carrier.  
     
     
         9 . The method of  claim 3  wherein the tumor antigen is carcinoembryonic antigen.  
     
     
         10 . The method of  claim 9  wherein the recombinant vaccinia virus is administered to the patient in admixture with a pharmaceuatically suitable carrier.  
     
     
         11 . The method of  claim 9  wherein said virus comprises at least one additional exogenous DNA sequence encoding human B7.  
     
     
         12 . The method of  claim 11  wherein the recombinant vaccinia virus is administered to the patient in admixture with a pharmaceutically suitable carrier.  
     
     
         13 . The method of  claim 3  wherein the tumor antigen is a human melanoma-associated antigen.  
     
     
         14 . The method of  claim 13  wherein the recombinant vaccinia virus is administered to the patient in admixture with a pharmaceutically suitable carrier.  
     
     
         15 . The method of  claim 13  wherein said virus comprises at least one additional exogenous DNA sequence encoding human B7.  
     
     
         16 . The method of  claim 15  wherein the recombinant vaccinia virus is administered to the patient in admixture with a pharmaceutically suitable carrier.