biostudies-literatureMoreira DNCI NIH HHSDepartment of Defense5948-5962https://www.ebi.ac.uk/biostudies/studies/S-EPMC6279477biostudies-literatureUnknown24(23)<h4>Purpose</h4>Prostate cancers show remarkable resistance to emerging immunotherapies, partly due to tolerogenic STAT3 signaling in tumor-associated myeloid cells. Here, we describe a novel strategy combining STAT3 inhibition with Toll-like Receptor 9 (TLR9) stimulation to unleash immune response against prostate cancers regardless of the genetic background.<h4>Experimental design</h4>We developed and validated a conjugate of the STAT3 antisense oligonucleotide (ASO) tethered to immunostimulatory TLR9 agonist (CpG oligonucleotide) to improve targeting of human and mouse prostate cancer and myeloid immune cells, such as myeloid-derived suppressor cells (MDSC).<h4>Results</h4>CpG-STAT3ASO conjugates showed improved biodistribution and potency of STAT3 knockdown in target cells <i>in vitro<Clinical cancer research : an official journal of the American Association for Cancer ResearchSTAT3 Inhibition Combined with CpG Immunostimulation Activates Antitumor Immunity to Eradicate Genetically Distinct Castration-Resistant Prostate Cancers.PMC6279477R01 CA213131P30 CA033572W81XWH-16-1-0499Swiderski PPal SKMoreira DZhang ZLu XSu YLWhite SVAdamus TDePinho RAZhao XKortylewski MfalseSTAT3 Inhibition Combined with CpG Immunostimulation Activates Antitumor Immunity to Eradicate Genetically Distinct Castration-Resistant Prostate Cancers.<h4>Purpose</h4>Prostate cancers show remarkable resistance to emerging immunotherapies, partly due to tolerogenic STAT3 signaling in tumor-associated myeloid cells. Here, we describe a novel strategy combining STAT3 inhibition with Toll-like Receptor 9 (TLR9) stimulation to unleash immune response against prostate cancers regardless of the genetic background.<h4>Experimental design</h4>We developed and validated a conjugate of the STAT3 antisense oligonucleotide (ASO) tethered to immunostimulatory TLR9 agonist (CpG oligonucleotide) to improve targeting of human and mouse prostate cancer and myeloid immune cells, such as myeloid-derived suppressor cells (MDSC).<h4>Results</h4>CpG-STAT3ASO conjugates showed improved biodistribution and potency of STAT3 knockdown in target cells <i>in vitro<2018-01-01T00:00:00Z2018 Dec2025-04-19T01:49:06.427Z2020-10-29T17:03:36ZS-EPMC62794773033727910.1158/1078-0432.CCR-18-127710.1158/1078-0432.ccr-18-1277