Equipping Natural Killer Cells with Specific Targeting and Checkpoint Blocking Aptamers for Enhanced Adoptive Immunotherapy in Solid Tumors.
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.
['Zhang|Da|D|0000-0002-2613-1354', 'Zheng|Youshi|Y|', 'Lin|Ziguo|Z|0000-0002-7939-2654', 'Liu|Xiaolong|X|0000-0002-3096-4981', 'Li|Juan|J|0000-0001-7175-2320', 'Yang|Huanghao|H|0000-0001-5894-0909', 'Tan|Weihong|W|']
D000818:Animals D017209:Apoptosis D052157:Aptamers, Nucleotide D060890:B7-H1 Antigen D059447:Cell Cycle Checkpoints D045744:Cell Line, Tumor D016207:Cytokines D006801:Humans D016219:Immunotherapy, Adoptive D007694:Killer Cells, Natural D051379:Mice D009336:Necrosis D009369:Neoplasms D023041:Xenograft Model Antitumor Assays
natural killer cells aptamers solid tumors PD1/PDL1 checkpoint blockade immunology