Abstract 4786: BP1003, a novel liposome-incorporated STAT3 antisense oligodeoxynucleotide inhibitor

• Published in: Cancer research (Chicago, Ill.) Ill.), 2019-07, Vol.79 (13_Supplement), p.4786-4786
• Main Authors: Dai, Bingbing, Ashizawa, Ana Tari, Augustine, Jithesh J., Kim, Michael, Fleming, Jason
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2019-4786

Background: Signal Transduction and Activator of Transcription-3 (STAT3), though typically inactive in normal cells, is aberrantly active in cancer cells. Activation of STAT3 has been found in many types of cancers, including non-small cell lung cancer (NSCLC), acute myelogenous leukemia (AML), and pancreatic ductal adenocarcinoma (PDAC). Activation of STAT3 correlates with poor clinical outcome, high grade disease and metastasis, and has been linked with resistance to chemotherapy, including gemcitabine, which is one of the standard of care agents for advanced PDAC. Therefore, inhibition of STAT3 in combination with chemotherapy is expected to produce clinical benefit. We have developed BP1003, a novel liposome-incorporated STAT3 antisense oligodeoxynucleotide (oligo) as a specific inhibitor of STAT3. Methods: Four candidate antisense oligo sequences directed against STAT3 mRNA were initially identified. They were manufactured as nuclease-resistant P-ethoxy oligos and incorporated into neutral dioleoylphosphatidylcholine liposomes. Cell viability tests and Western blots were conducted to determine the inhibitory effects of liposome-incorporated STAT3 antisense oligo on NSCLC and AML cells. Ex vivo live tissue sensitivity assay (LTSA) was performed with a panel of 20 PDAC patients-derived xenografts (PDXs) to study the overall activity of BP1003, alone and in combination with gemcitabine. Using previous defined criteria, tissue slice viability inhibition greater than 30% and p