131 Niclosamide-derived immune modulator to enhance immunotherapy for triple-negative breast cancer

Abstract

Objectives/Goals: Triple-negative breast cancer (TNBC) is a highly aggressive and prevalent breast cancer subtype that lacks targeted therapies. This study aims to investigate whether the niclosamide derivative HJC0152 can modulate tumor-derived PD-L1 expression and enhance the effectiveness of anti-PD-1 immunotherapy in treating TNBC. Methods/Study Population: Niclosamide derivative HJC0152 was developed as a novel cancer therapeutic and immunomodulating agent. Human TNBC cell line (MDA-MB-231) was treated with HJC0152, and activation of the STAT3 signaling pathway was evaluated using Western blotting. RNA-Seq was employed to analyze the expression of protein-coding genes, particularly those related to immune response. To study therapeutic potential in vivo, TNBC mouse models will be treated with single agent treatments as well as a combination therapy of HJC0152 and anti-PD-1. Tumor volume and mass will be measured over time to determine growth inhibition. Results/Anticipated Results: Preliminary studies indicate that HJC0152 exhibits enhanced solubility compared to Niclosamide, along with high anticancer potency both in vitro and in vivo. HJC0152 was found to effectively inhibit the activation of phosphorylated STAT3 (p-STAT3) in MDA-MB-231 cells, a key signaling pathway associated with cancer progression and immune evasion. RNA-Seq analysis of HJC0152-treated MDA-MB-231 cells revealed a decrease in PD-L1 expression, an essential immune checkpoint protein involved in tumor immune suppression. These findings suggest that HJC0152 is a promising immune modulator that may enhance the efficacy of immune checkpoint blockade therapy for TNBC. Discussion/Significance of Impact: This study explores an innovative immunotherapy for TNBC using the Niclosamide derivative HJC0152, which inhibits STAT3 signaling and downregulates PD-L1. Results from this study will provide a foundation for HJC0152’s inclusion in clinical trials and potentially offer a new and promising therapeutic option for TNBC treatment.