Cancer treatment and diagnosis

Abstract

The present disclosure provides, in general, a method for selecting a therapy for treating cancer in a human subject and subsequently treating cancer in a subject, which includes isolating a cancer cell from a human subject having cancer, determining the functional activity of the innate immune regulator STimulator of INterferon Genes (STING) or the cellular nucleotidyltransferase, cyclic Guanosine Monophosphate (cGMP)—Adenosine Monophosphate (AMP) Synthase (cyclicGMP-AMP Synthase or cGAS) in the cell, and selecting a therapy for the cancer based on the functional activity of the STING or cGAS in the cell. Also provided, if the functional activity of STING and/or cGAS is determined to be defective in the cell, the therapy selected is one that is effective at killing STING-deficient and/or cGAS-deficient cancer cells, for example a therapy including administering to the subject an oncolytic virus.

What is claimed: 
     
         1 . A method for treating a cancer with an oncolytic virus:
 a) performing a PCR assay on a sample from a mammal to determine if the mammal has a defective functional activity of Stimulator of Interferon Genes (STING) in a cell population in the sample;   b) if the mammal has a defective functional activity of STING, then identifying a selected therapy, where the selected therapy is administering one or more oncolytic viruses having a double stranded (ds) deoxynucleic acid (DNA) (dsDNA) genome selected from the group consisting of herpes simplex virus, Varicella Zoster virus, and vaccinia virus; and   c) internally treating the mammal with the selected therapy.   
     
     
         2 . The method of  claim 1 , where the functional activity of STING is determined to be defective based at least in part on the amount of cyclic Guanosine Monophosphate (cGMP)—Adenosine Monophosphate (AMP) Synthase (cGAS) in the cell population. 
     
     
         3 . The method of  claim 2 , where the functional activity of STING is determined to be defective when an immune response in the mammal is enhanced by administration of the one or more oncolytic viruses are selected from the group consisting of herpes simplex virus-1 γ 1 34.5 deletion and vaccinia virus vTF7-3. 
     
     
         4 . The method of  claim 3 , where the immune response includes modulation of T cell activity, modulation of dendritic cell activity, and modulation of immune cytokines. 
     
     
         5 . The method of  claim 2 , further comprising where the functional activity of STING is determined to be defective based at least in part on determining a cellular level of one or more mRNA's selected from the group consisting of Interleukin-1 (IL-1), IL-3, IL-18 and IL-22 in the cell population. 
     
     
         6 . The method of  claim 5 , where the cancer is a colorectal adenocarcinoma and the selected therapy comprises administering to the subject the oncolytic virus HSV1k34.5, where the oncolytic virus induces the production of interferons in the mammal. 
     
     
         7 . The method of  claim 1 , further comprising where the functional activity of STING is determined to be defective based at least in part on determining the cellular level of interleukin-22 binding proteins in the cell population. 
     
     
         8 . The method of  claim 7 , further comprising where the functional activity of STING is determined to be defective based at least in part on determining the cellular level of Interleukin-1 (IL-1), IL-18 and IL-22 in the cell population. 
     
     
         9 . The method of  claim 1 , where the selected therapy is administration of dsDNA in combination with interferon-beta. 
     
     
         10 . The method of  claim 1 , further comprising if the sample does not have the defective functional activity of STING, administering a cancer treatment to the subject that does not cause a DNA mutation. 
     
     
         11 . The method of  claim 1 , where the cancer is colitis-associated cancer. 
     
     
         12 . The method of  claim 1 , where an immune response in the cancer that has the defective functional activity of STING is enhanced by administration of the one or more oncolytic viruses selected from the group consisting of herpes simplex virus-1 γ 1 34.5 deletion and vaccinia virus vTF7-3. 
     
     
         13 . The method of  claim 1 , where the therapy results in increased tumor cell death and/or retarded tumor growth. 
     
     
         14 . The method of  claim 1 , where the sample is selected from the group consisting of a body fluid, a cell sample, a tissue sample, a biopsy sample, a tissue print, a skin sample, and a hair sample. 
     
     
         15 . The method of  claim 14 , where the body fluid is selected from the group consisting of blood, urine, plasma, saliva, or cerebrospinal fluid. 
     
     
         16 . The method of  claim 1 , where the sample is a soluble fraction of a cell preparation, where the cells are grown in cell culture in vitro and the media from the cell culture is tested for functional activity of STING. 
     
     
         17 . A method for treating a cancer comprising:
 a) determining whether a mammal having one or more of colorectal cancer, colon cancer and melanoma cancer has a defective functional activity of cyclic Guanosine Monophosphate (cGMP)—Adenosine Monophosphate (AMP) Synthase (cGAS) by performing a PCR assay on a sample of the mammal to determine a cellular levels of one or more mRNA's selected from the group consisting of Interleukin-1 (IL-1), IL-3, IL-18 and IL-22 to determine if a cell population has a defective functional activity of cGAS;   b) if the mammal has the defective functional activity of cGAS, then selecting a therapy for the cancer, where the therapy involves administering one or more oncolytic viruses having a double stranded (ds) deoxynucleic acid (DNA) (dsDNA) genome selected from the group consisting of herpes simplex virus and vaccinia virus, and   c) administering the selected therapy to the mammal.   
     
     
         18 . The method of  claim 17 , where the functional activity of cGAS is defective if an immune response in the mammal is enhanced by administration of the one or more oncolytic viruses are selected from the group consisting of herpes simplex virus-1 γ 1 34.5 deletion and vaccinia virus vTF7-3. 
     
     
         19 . A method for treating a cancer comprising:
 a) determining whether a mammal having one or more of colorectal cancer, colon cancer and melanoma cancer that has failed at least one chemotherapy regimen has a defective functional activity of cyclic Guanosine Monophosphate (cGMP)—Adenosine Monophosphate (AMP) Synthase (cGAS) measured by performing a first PCR assay on a first sample of the mammal to determine if one or more mRNA's selected from the group consisting of Interleukin-1 (IL-1), IL-3, IL-18 and IL-22 is lowered;   b) if the mammal has the defective functional activity of cGAS, then performing a first oncolytic therapy of administering one or more oncolytic viruses selected from the group consisting of herpes simplex virus-1 γ 1 34.5 deletion and vaccinia virus vTF7-3;   c) performing a second PCR assay on a second sample of the mammal to determine if one or more mRNA's selected from the group consisting of IL-1, IL-3, IL-18 and IL-22 remains lowered to determine whether the mammal continues to have a defective functional activity of cGAS; and   d) i) if the mammal continues to have the defective functional activity of cGAS, then performing a second oncolytic therapy comprising administering one or more oncolytic viruses selected from the group consisting of herpes simplex virus, Varicella Zoster virus, and vaccinia virus; or
 ii) if the mammal has normal cellular levels of IL-1, IL-3, IL-18 and IL-22 mRNA's, then performing a second oncolytic therapy comprising administering a second agent that can increase cGAS levels in the subject. 
   
     
     
         20 . The method of  claim 19 , where in step d) i) the one or more oncolytic viruses are administered in conjunction with a third agent.