Fmrp and cancer treatment

Abstract

The present invention provides compositions and methods for down-modulating the expression and/or the immuno-suppressive activity of i) the FMRP protein, ii) an mRNA encoding the FMRP protein, and/or iii) the FMR1 gene for the treatment and/or prevention of primary cancer and/or cancer metastasis in a subject in need thereof.

1 - 20 . (canceled) 
     
     
         21 . A method of identifying an agent that modulates the expression and/or activity of i) the FMRP protein activity, ii) an mRNA encoding FMRP and/or iii) the FMR1 gene, the method comprising:
 (1) providing a sample expressing FMRP;   (2) contacting the biological sample with a test agent;   (3) determining the level of expression of and/or activity of FMRP;   (4) comparing the level of expression and/or activity with a control sample not contacted by the test agent; and   (5) selecting a test agent that decreases the level of expression of and/or activity of FMRP.   
     
     
         22 . The method according to  claim 21 , wherein the level of expression of and/or activity of FMRP is determined by the agent disrupting the binding of by FMRP to its target mRNAs, miRNAs, or proteins. 
     
     
         23 . The method according to  claim 21 , wherein said agent inhibits the translation of an RNA encoding FMRP. 
     
     
         24 . The method according to  claim 21 , wherein the agent inhibits the transcription of the FMR1 gene encoding FMRP. 
     
     
         25 . The method according to  claim 21 , wherein the agent inhibits or impairs the binding of the FMRP to a target mRNA or miRNA. 
     
     
         26 . An agent identified by the method according to  claim 21 . 
     
     
         27 . The agent according to  claim 26 , wherein the agent is a chemical compound, a peptide or analog thereof, an antibody or an antigen-binding fragment of said antibody, antibody mimetic, or a nucleic acid. 
     
     
         28 . The agent according to  claim 27 , wherein the agent is a nucleic acid is selected from the group comprising an nucleic acid encoding an miRNA, an siRNA, a piRNA, an hnRNA, an snRNA, an sg RNA, CRISPR-based loss-of-function system, an esiRNA, an shRNA, and an antisense oligonucleotide, a peptide or analog thereof, an antibody or an antigen-binding fragment of said antibody, an antibody mimetic, or a combination thereof. 
     
     
         29 . A plasmid or a vector comprising one or more nucleic acid(s) according to  claim 28 . 
     
     
         30 . A host cell comprising a plasmid or vector according to  claim 29 . 
     
     
         31 . A host cell comprising one or more nucleic acid(s) according to  claim 28 . 
     
     
         32 . The agent according to  claim 27 , wherein the agent is a chemical compound. 
     
     
         33 . A pharmaceutical composition comprising:
 i) a therapeutically effective amount of an agent according to  claim 26 , or   ii) a plasmid or a vector of  claim 29 , or   iii) a host cell of  claim 30  or  31 , and   a pharmaceutically acceptable carrier or diluent.   
     
     
         34 . A method for the treatment of cancer and/or the treatment and/or prevention of a cancer metastasis in a subject in need thereof, the method comprising administering to the subject the pharmaceutical composition according to  claim 33 . 
     
     
         35 . The method according to  claim 34 , further comprising administering one or more anti-cancer therapy. 
     
     
         36 . The method according to  claim 35 , wherein the one or more anti-cancer therapy comprises a therapeutically effective amount of an immune checkpoint inhibitor. 
     
     
         37 . The method according to  claim 35 , wherein the immune checkpoint inhibitor is selected from the group comprising a PD-1 inhibitor, a PD-L1 inhibitor, and a CTLA-4 inhibitor, or a combination thereof. 
     
     
         38 . The method according to  claim 35 , wherein the one or more anti-cancer therapy is included in combination with a therapeutically effective amount of an anti-tumor-vaccine, including personalized neo-antigen cocktails, or other immune-stimulatory agents that bolster anti-tumor immune responses.