# US 9,752,145 B2 · Compositions and methods for reducing C/EBP homologous protein activity in myeloid-derived suppressor cells > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 9,752,145 B2 - Document ID: US9752145B2 - Status: Granted - Kind: B2 - Application number: 15/125,737 - Filed: 2015-03-16 - Published: 2017-01-05 - Granted: 2017-09-05 - Earliest claimed: 2014-03-17 - Assignees: Board of Supervisors of Louisiana State University and Agricultural and Mechanical College - Applicants: Board of Supervisors of Louisiana State University and Agricultural and Mechanical College - Inventors: Paulo Cesar Rodriguez; Augusto C. Ochoa - Web page: https://patentgrep.com/patent/US9752145B2 ## CPC - C12N 15/113: Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; {Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing (when used in plants C12N15/8218)} - A61K 9/1271: Non-conventional liposomes, e.g. PEGylated liposomes or liposomes coated or grafted with polymers (liposomes as conjugates {A61K47/6911}) - C12N 2310/14: interfering nucleic acids [NA] - C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00) - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) ## Abstract Provided are compositions and methods of use thereof that modulate C/EBP homologous stress-related protein (Chop) activity in Myeloid-derived Suppressor Cells (MDSCs). Chop is a key point in the response of MDSCs to tumor-generated stress factors. In turn, the MDSCs release cytokines and other factors that function as immune suppressors, thereby allowing the tumors to thrive and expand. By inhibiting the level of Chop activity, the immunosuppressive function of MDSCs is disrupted. It has also been unexpectedly found that there is a concomitant increase in the ability of MDSCs to act as antigen-presenting and cytokine producing cells so as to act in increasing the efficacy of anti-tumor immune-based therapies. ## Claims ### Claim 1 A method of reducing the level of activity of C/EBP-homologous protein (Chop) in a myeloid-derived suppressor cell (MDSC) or population of said cells, said method comprising delivering to a recipient MDSC or population of said recipient cells a composition comprising an siRNA, wherein the siRNA is an isolated double-stranded ribonucleic acid (dsRNA) molecule having either no overhang regions or at least one overhang region, wherein each overhang region contains six or fewer nucleotides, and wherein the dsRNA inhibits expression by a cell of a Chop protein, and wherein a first strand of the dsRNA is substantially identical to the sequence according to SEQ ID NO: 1, and a second strand is substantially complementary to the first that reduces the activity of Chop in the cell(s), and a vehicle for delivery of the agent to the interior of the recipient cell. ### Claim 2 (depends on 1) The method of claim 1, wherein the agent is an siRNA and results in gene silencing of the Chop gene in the recipient MDSC or population of MDSCs. ### Claim 3 (depends on 1) The method of claim 1, wherein the first strand of the dsRNA has a nucleotide sequence comprising SEQ ID NO: 1. ### Claim 4 (depends on 1) The method of claim 1, wherein the vehicle is a liposome. ### Claim 5 (depends on 1) The method of claim 1, wherein the vehicle is a pegylated-liposome. ### Claim 6 (depends on 1) The method of claim 1, wherein the composition further comprises a pharmaceutically acceptable carrier. ### Claim 7 (depends on 1) The method of claim 1, wherein the recipient MDSC or population of said recipient cells are isolated from an animal or human subject. ### Claim 8 (depends on 7) The method of claim 7, wherein the isolated MDSC or population of said recipient cells are cultured cells. ### Claim 9 A composition comprising an siRNA agent that when delivered to a myeloid-derived suppressor cell (MDSC) or population of said cells reduces the level of expression of a Chop-encoding gene, thereby reducing the level of Chop in the cell or cells, wherein the siRNA is an isolated double-stranded ribonucleic acid (dsRNA) molecule having either no overhang regions or at least one overhang region, wherein each overhang region contains six or fewer nucleotides, and wherein the dsRNA inhibits expression by a cell of a Chop protein, and wherein a first strand of the dsRNA is substantially identical to the sequence according to SEQ ID NO: 1, and a second strand is substantially complementary to the first. ### Claim 10 (depends on 9) The composition of claim 9, further comprising a vehicle suitable for the delivery of the agent to the interior of the cell or cells. ### Claim 11 (depends on 10) The composition of claim 10, wherein the vehicle is a liposome. ### Claim 12 (depends on 10) The composition of claim 10, wherein the vehicle is a pegylated-liposome. ### Claim 13 (depends on 9) The composition of claim 9, wherein the first strand of the dsRNA has the nucleotide sequence SEQ ID NO: 1.