Graduate Student Oral Session (I) (English)
[O7-13]
Polymeric Nanoparticles Enable CRISPR/Cas9-Mediated CD24 Silencing to Enhance Immunotherapy in Triple-Negative Breast Cancer
발표자ZHANG ZHENGZHENG (Chonnam National University)
연구책임자남주택 (Chonnam National University)
Abstract
Immune evasion and limited response to immunotherapy remain major challenges in triple-negative breast cancer (TNBC). CD24 is highly expressed on tumor cells and interacts with Siglec-10 on immune cells, which suppresses macrophage-mediated phagocytosis and makes it a potential immune checkpoint (ICB) target. Herein, we developed a polyethyleneimine (PEI) based nanoparticle system (PDGCS) to deliver CRISPR/Cas9 plasmid for targeted CD24 gene silencing. Our PDGCS nanoparticles enable stable gene delivery and efficient intracellular genome editing, which effectively block the CD24-Siglec-10 signaling. Consequently, enhanced phagocytosis by tumor-associated macrophages. Moreover, CD24 knockdown significantly improve the therapeutic efficacy of ICB immunotherapy in vivo. This study demonstrates a safe and effective polymeric CRISPR delivery platform and provides a promising strategy for synergistic immunotherapy in TNBC.