Immunomodulatory rna

Abstract

The present invention includes methods for detecting cancer in a subject and measuring the effectiveness of a cancer treatment. In certain embodiments, the invention includes assessing the level of unshielded RN7SL1 RNA in a sample from a subject.

What is claimed: 
     
         1 . A method of detecting and treating a cancer in a subject, the method comprising:
 assessing the level of unshielded RN7SL1 RNA in a sample from the subject,   comparing the level of unshielded RN7SL1 RNA from the subject to a reference sample, wherein the reference is an otherwise identical non-cancerous sample from a subject,   wherein when the level of unshielded RN7SL1 RNA from the subject is higher than the control sample, the subject has cancer, and   treatment of the cancer in the subject is recommended.   
     
     
         2 . The method of  claim 1 , wherein the subject is a human. 
     
     
         3 . The method of  claim 1 , wherein the sample is selected from the group consisting of blood, serum, plasma, biopsy, or tumor. 
     
     
         4 . The method of  claim 1 , wherein the cancer comprises breast cancer. 
     
     
         5 . The method of  claim 1 , wherein assessing the RNA levels comprises a method selected from the group consisting of RNA sequencing, microarray, and qRT-PCR. 
     
     
         6 . The method of  claim 1 , wherein the treatment comprises surgery, chemotherapy, immunotherapy, targeted therapy, immune checkpoint blockade (ICB) therapy, or radiotherapy. 
     
     
         7 . The method of  claim 1 , wherein the treatment comprises administering at least one therapeutic agent selected from the group consisting of an anti-PD-1 antibody, an anti-PD-L1 antibody, an anti-CTLA-4 antibody, a CSF1R inhibitor, an anti-CSF1R antibody, a small molecule inhibitor of CSF1R, e.g., BLZ945, anti-TIM-3 antibody molecule, or an anti-LAG-3 molecule an IL-13 inhibitor, an IL-4 inhibitor, an IL-13Rα1 inhibitor, an IL-4Rα inhibitor, an IL-10 inhibitor, a CSF-1 inhibitor, a TGF beta inhibitor, a JAK2 inhibitor, a cell surface molecule, an iron oxide, a small molecule inhibitor, a PI3K inhibitor, an HDAC inhibitor, an inhibitor of the glycolytic pathway, a mitochondria-targeted antioxidant, a clodronate liposome, a Flt3 ligand polypeptide, or any combination thereof. 
     
     
         8 . A method of detecting and treating a cancer in a subject, the method comprising:
 assessing the level of unshielded RN7SL1 RNA in a sample from the subject,   assessing the level of shielded RN7SL1 RNA in the sample from the subject, comparing the level of unshielded RN7SL1 RNA to the level of shielded RN7SL1 RNA,   wherein when the level of unshielded RN7SL1 RNA from the subject is higher than the level of shielded RN7SL1 RNA, the subject has cancer, and   treatment of the cancer in the subject is recommended.   
     
     
         9 . The method of  claim 8 , wherein the subject is a human. 
     
     
         10 . The method of  claim 8 , wherein the sample is selected from the group consisting of: blood, serum, plasma, biopsy, or tumor. 
     
     
         11 . The method of  claim 8 , wherein the cancer comprises breast cancer. 
     
     
         12 . The method of  claim 8 , wherein assessing the RNA levels comprises a method selected from the group consisting of: RNA sequencing, microarray, and qRT-PCR. 
     
     
         13 . The method of  claim 8 , wherein the treatment comprises surgery, chemotherapy, immunotherapy, targeted therapy, immune checkpoint blockade (ICB) therapy, or radiotherapy. 
     
     
         14 . The method of  claim 8 , wherein the treatment comprises administering at least one therapeutic agent selected from the group consisting of an anti-PD-1 antibody, an anti-PD-L1 antibody, an anti-CTLA-4 antibody, a CSF1R inhibitor, an anti-CSF1R antibody, a small molecule inhibitor of CSF1R, e.g., BLZ945, anti-TIM-3 antibody molecule, or an anti-LAG-3 molecule an IL-13 inhibitor, an IL-4 inhibitor, an IL-13Rα1 inhibitor, an IL-4Rα inhibitor, an IL-10 inhibitor, a CSF-1 inhibitor, a TGF beta inhibitor, a JAK2 inhibitor, a cell surface molecule, an iron oxide, a small molecule inhibitor, a PI3K inhibitor, an HDAC inhibitor, an inhibitor of the glycolytic pathway, a mitochondria-targeted antioxidant, a clodronate liposome, a Flt3 ligand polypeptide, or any combination thereof. 
     
     
         15 . A method of treating a cancer in a subject in need thereof, the method comprising, administering to the subject a therapeutically effective amount of an unshielded RN7SL1 RNA. 
     
     
         16 . The method of  claim 15 , further comprising administering an additional treatment to the subject, wherein the additional treatment is selected from the group consisting of surgery, chemotherapy, immunotherapy, targeted therapy, immune checkpoint blockade (ICB) therapy, or radiotherapy. 
     
     
         17 . The method of  claim 16 , wherein the additional treatment comprises administering at least one therapeutic agent selected from the group consisting of an anti-PD-1 antibody, an anti-PD-L1 antibody, an anti-CTLA-4 antibody, a CSF1R inhibitor, an anti-CSF1R antibody, a small molecule inhibitor of CSF1R, e.g., BLZ945, anti-TIM-3 antibody molecule, or an anti-LAG-3 molecule an IL-13 inhibitor, an IL-4 inhibitor, an IL-13Rα1 inhibitor, an IL-4Rα inhibitor, an IL-10 inhibitor, a CSF-1 inhibitor, a TGF beta inhibitor, a JAK2 inhibitor, a cell surface molecule, an iron oxide, a small molecule inhibitor, a PI3K inhibitor, an HDAC inhibitor, an inhibitor of the glycolytic pathway, a mitochondria-targeted antioxidant, a clodronate liposome, a Flt3 ligand polypeptide, or any combination thereof. 
     
     
         18 . The method of  claim 15 , wherein the unshielded RN7SL1 RNA is administered to the tumor microenvironment of the subject. 
     
     
         19 . The method of  claim 15 , wherein the RN7SL1 RNA comprises SEQ ID NO: 2. 
     
     
         20 . A method of treating a subject having cancer comprising assessing the aggressiveness of the cancer, the method comprising:
 assessing the level of unshielded RN7SL1 RNA in a sample from the subject,   comparing the level of unshielded RN7SL1 RNA from the subject to a reference sample, wherein the reference is an otherwise identical non-cancerous sample from a subject,   wherein when the level of unshielded RN7SL1 RNA from the subject is higher than the control sample, the cancer is aggressive, and   the subject is treated with an aggressive cancer therapy.   
     
     
         21 . A method of treating a subject having cancer comprising assessing the aggressiveness of the cancer, the method comprising:
 assessing the level of unshielded RN7SL1 RNA in a sample from the subject,   assessing the level of shielded RN7SL1 RNA in the sample from the subject, comparing the level of unshielded RN7SL1 RNA to the level of shielded RN7SL1 RNA,   wherein when the level of unshielded RN7SL1 RNA from the subject is higher than the shielded RN7SL1 RNA, the cancer is aggressive, and   the subject is treated with an aggressive cancer therapy.   
     
     
         22 . A method of determining whether treatment in a subject should be altered because the subject is resistant to a therapy selected from the group consisting of chemotherapy, radiation, and targeted therapy, the method comprising:
 assessing the level of unshielded RN7SL1 RNA in a sample from the subject,   comparing the level of unshielded RN7SL1 RNA from the subject to a reference sample, wherein the reference is an otherwise identical non-cancerous sample from a subject,   wherein when the level of unshielded RN7SL1 RNA from the subject is higher than the control sample, the subject is resistant to the therapy, and   altering the subject's treatment so as to provide benefit to the subject.   
     
     
         23 . A method of treating a subject having cancer comprising predicting whether a subject will respond to an immunotherapy treatment, the method comprising:
 assessing the level of unshielded RN7SL1 RNA in a sample from the subject,   comparing the level of unshielded RN7SL1 RNA from the subject to a reference sample, wherein the reference is an otherwise identical non-cancerous sample from a subject,   wherein when the level of unshielded RN7SL1 RNA from the subject is higher than the control sample, the subject is predicted to respond to immunotherapy, and   treating the subject with the immunotherapy.   
     
     
         24 . A method of treating a subject having cancer comprising measuring the effectiveness of an immunotherapy treatment in the subject, the method comprising:
 administering to the subject an immunotherapy treatment,   assessing the level of unshielded RN7SL1 RNA in a sample from the subject,   comparing the level of unshielded RN7SL1 RNA from the subject to a reference sample, wherein the reference is an otherwise identical non-cancerous sample from a subject,   wherein when the level of unshielded RN7SL1 RNA from the subject is higher than the control sample, the immunotherapy treatment is deemed effective, and   immunotherapy treatment is continued in the subject.