NO-Shielded T Cells for Enhanced Antitumor Immunotherapy
발표자
이지혜 (포항공과대학교)
연구책임자
김원종 (포항공과대학교)
공동저자
이지혜 (포항공과대학교), 김원종 (포항공과대학교)
초록
내용
Adoptive T-cell therapy relies on robust cytotoxic T-cell activity, yet the tumor microenvironment (TME) frequently enforces immunosuppression that drives T-cell hyporesponsiveness and cell death. Among diverse suppressive cues, nitric oxide (NO) is commonly enriched in tumors and contributes to impaired T-cell signaling and survival. Here, we present a strategy to locally neutralize NO at the T-cell interface by installing NO-reactive components directly onto the T-cell plasma membrane. We developed a membrane-fusible liposomal platform, termed LipoNOX, formulated with o-phenylenediamine–bearing lipids and a cationic helper lipid (DOTAP), which stably inserts into the cell membrane and limits NO buildup in T cells exposed to tumor-like conditions. This membrane-anchored NO capture reduces NO-driven protein damage, including S-nitrosylation and tyrosine nitration, thereby preserving key activation pathways.