Journal
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
Volume 59, Issue 29, Pages 12022-12028Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.202002145
Keywords
aptamers; immunology; natural killer cells; PD1; PDL1 checkpoint blockade; solid tumors
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Funding
- Natural Science Foundation of China [91959102, 21635002, 61805041]
- Natural Science Foundation of Fujian Province of China [2017J06004]
- Shanghai Rising-Star Program [19QA1405400]
- Program for Changjiang Scholars and Innovative Research Team in University [IRT15R11]
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Herein, we propose an aptamer-equipping strategy to generate specific, universal and permeable (SUPER) NK cells for enhanced immunotherapy in solid tumors. NK cells were chemically equipped with TLS11a aptamer targeting HepG2 cells and PDL1-specific aptamer without genetic alteration. The dual aptamer-equipped NK cells exhibited high specificity to tumor cells, resulting in higher cytokine secretion and apoptosis/necrosis compared to parental or single aptamer-equipped NK cells. Interestingly, dual aptamer-equipped NK cells induced remarkable upregulation of PDL1 expression in HepG2 cells, enhancing checkpoint blockade. Furthermore, in vivo intravital imaging demonstrated high infiltration of aptamer-equipped NK cells into deep tumor region, leading to enhanced therapeutic efficacy in solid tumors. This work offers a straightforward chemical strategy to equip NK cells with aptamers, holding considerable potential for enhanced adoptive immunotherapy in solid tumors.
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