Natural killer (NK) cells are a type of immune cell. They can kill cancer and virally infected cells. This is used in NK-based immunotherapy to treat hematological malignancies, i.e., cancers that affect the blood, bone marrow, or lymph nodes. However, targeting specific solid tumors using NK cells is challenging.
Juan Li, Fuzhou University, China, and The Cancer Hospital of the University of Chinese Academy of Sciences, Hangzhou, Huanghao Yang, Fuzhou University, and colleagues have developed a strategy to enhance the efficacy of NK cells. The team prepared specific, universal, and permeable (or “SUPER”) NK cells by binding aptamers to NK cell membranes. Aptamers are short DNA or RNA strands or peptides that can selectively bind to a specific target. The team used the aptamers TLS11a and PDL1. TLS11a targets hepatocellular carcinoma (HCC) liver cancer cells. PDL1 blocks the activity of PD1/PDL1 immune checkpoint proteins and, thereby, boosts immune activity against cancer cells. The aptamers were bound to the cell membrane using a click reaction.
The resulting “SUPER” NK cells target liver tumor cells and could be used for enhanced immunotherapy against solid tumors. In addition to the selective targeting and PDL/PDl-1 blocking, the cells secrete interferon-γ (IFNγ), an immunity-related protein that can suppress tumor growth. The used aptamers are low in cost and can be synthesized on a large scale, and the aptamer-equipped NK cells are biocompatible and biodegradable. The cells’ target could be changed to other solid tumors of interest by simply changing the aptamers.
- Equipping Natural Killer Cells with Specific Targeting and Checkpoint Blocking Aptamers for Enhanced Adoptive Immunotherapy in Solid Tumors,
Da Zhang, Youshi Zheng, Ziguo Lin, Xiaolong Liu, Juan Li, Huanghao Yang, Weihong Tan,
Angew. Chem. Int. Ed. 2020.