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·2026
Engineering T Cells with Membrane-Anchored Nitric Oxide Scavengers for Anticancer Therapy
Jihye Lee, Yeoul Kang, Seonwoo Kang, Hyungjin Sun, Heeyeon Yoon, Junsang Doh, Won Jong Kim
ACS Nano
초록

T cells are fundamental for orchestrating cancer-specific cytotoxic responses that are central to the success of immune-activation-related cancer therapy. However, the immunosuppressive tumor microenvironment (TME) undermines the effectiveness of T cell therapy by inducing dysfunction and promoting apoptosis of infiltrated T cells. Considering that nitric oxide (NO) is abundantly present in the immunosuppressive TME and acts as a mediator of T cell dysfunction, we aimed to modulate the NO levels within the local T cell environment to enhance the efficacy of T cell therapy. We designed membrane-fusible NO-scavenging liposomes (Lipo<sup>NOX</sup>) to regulate intracellular NO accumulation in T cells within the TME. Lipo<sup>NOX</sup>, which is composed of <i>o</i>-phenylenediamine-containing lipids and 1,2-dioleoyl-3-trimethylammonium-propane, effectively integrated into the plasma membrane and protected the T cells from NO-mediated protein modifications, including S-nitrosylation and tyrosine nitration. Lipo<sup>NOX</sup>-engineered T cells (NOX-T cells) exhibited a revival of proliferation and activation in immunosuppressive TME-mimicking <i>in vitro</i> conditions without compromising their physiological integrity. This functionality significantly augmented the efficacy of T cell therapy in the B16-F10-OVA mouse model of tumor by increasing the population and activity of tumor-infiltrating T cells, thus providing a solid foundation for strategies targeting NO modulation in T cells.

키워드
Cytotoxic T cellT cellNitric oxideTumor microenvironmentIntracellularApoptosisCellPopulation
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2026

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