Equipping Natural Killer Cells with Specific Targeting and Checkpoint Blocking Aptamers for Enhanced Adoptive Immunotherapy in Solid Tumors.

Abstract

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.

• Authors: Da Zhang, Youshi Zheng, Ziguo Lin, Xiaolong Liu, Juan Li, Huanghao Yang, Weihong Tan
• Journal: Angewandte Chemie (International ed. in English) (Angew Chem Int Ed Engl) Vol. 59 Issue 29 Pg. 12022-12028 (07 13 2020) ISSN: 1521-3773 [Electronic] Germany
• PMID: 32246555 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chemical References

• Aptamers, Nucleotide
• B7-H1 Antigen
• CD274 protein, human
• Cytokines

Topics

• Animals
• Apoptosis (drug effects)
• Aptamers, Nucleotide (pharmacology)
• B7-H1 Antigen (biosynthesis, genetics)
• Cell Cycle Checkpoints (drug effects)
• Cell Line, Tumor
• Cytokines (metabolism)
• Humans
• Immunotherapy, Adoptive (methods)
• Killer Cells, Natural (drug effects)
• Mice
• Necrosis
• Neoplasms (therapy)
• Xenograft Model Antitumor Assays