Membrane-immobilized Gemcitabine for Cancer-Targetable NK cell Surface Engineering
발표자
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초록
내용
Although natural killer (NK) cell-based adoptive cell transfer (ACT) has shown promise in cancer immunotherapy, its efficacy against solid tumors is limited in tumor microenvironment. To overcome limitations, we developed membrane-immobilized gemcitabine (Gem) conjugates that can be easily anchored onto NK cell surfaces. Our results demonstrated that delivery of Gem by lipid-Gem coated NK (GCNK) cells could enhance antitumor efficacy through the following steps: 1) NK cells recognize and attack cancer cells, 2) upon cancer cell lysis, released Gem from GCNK cells is simultaneously delivered to the target cells, 3) Gem upregulates MHC class I-related chain A and B on cancer cells, thereby 4) boosting NK cell-mediated antitumor efficacy. Co-delivery of membrane-immobilized Gem with NK cells could achieve both immune synapse-mediated cancer recognition and sufficient chemotherapeutic effects, suggesting a promising immunotherapy to overcome low anticancer efficacies of conventional ACTs.