Abstract

Natural killer (NK) cells are innate immune cells that can be activated rapidly to target abnormal and virus-infected cells without prior sensitization. With significant advancements in cell biology technologies, many NK cell lines have been established. Among these cell lines, NK-92 cells are not only the most widely used but have also been approved for clinical applications. Additionally, chimeric antigen receptor-modified NK-92 cells (CAR-NK-92 cells) have shown strong antitumor effects. In this review, we summarize established human NK cell lines and their biological characteristics, and highlight the applications of NK-92 cells and CAR-NK-92 cells in tumor immunotherapy.

Highlights

  • Natural killer (NK) cells are innate immune cells that were first discovered in mice in 1975 [1]

  • The results showed that chimeric antigen receptor (CAR)-NK cells had in vivo activities similar to those of as CAR-T cells, but with less toxicity

  • CAR-NK-92 cells have many advantages, as follows: (1) CAR-NK-92 cells can target tumor cells and directly activate NK-92 cells to kill target cells; (2) even if the targeted antigen on the tumor is rapidly lost, the CAR-NK-92 cells can still be activated by their activating receptors [8]; (3) the inhibitory receptors are expressed at low levels on the surface [37] and deletion of inhibitory receptors makes NK-92 cells more resistant to solid tumors than other immune cells; and (4) NK-92 cells are immortalized cell lines with a uniform phenotype, allowing them to be cultured in vitro for a long time to proliferate

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Summary

Introduction

Natural killer (NK) cells are innate immune cells that were first discovered in mice in 1975 [1]. Allogeneic NK cells can be obtained from many sources, such as bone marrow, human embryonic stem cells, induced pluripotent stem cells, PB, and umbilical cord blood. These NK cells are difficult to purify and expand in vitro. All of these cell lines are characterized by a uniform phenotype, high purity, and function, consistent with the general characteristics of NK cells These cells can be cultured at a large scale in vitro, providing sufficient cells for research and clinical applications. RReecceeppttoorr DDiissttrriibbuuttiioonn aanndd KKiilllliinngg MMeecchhaanniissmm ooff NNKK CCeellllss. These two cell subclones do not mediate ADCC These cell lines can kill 721.221 cells with high expression of B7.1 [29]. Cytotoxicity analysis showed that YT2C2 and YTC3 cells primarily rely on cell surface receptor-mediated cytotoxicity

NKL Cells
HANK1 Cells
NK-YS Cells
KHYG-1 Cells
SNK-6 and SNT-8 Cells
IMC-1 Cells
NK-92 Cells
Progress in the Application of NK-92 Cells
Structure of CARs and Their Applications in NK-92 Cells
Preclinical Studies of CAR-NK-92 Cells
Ongoing Clinical Trials
Advantages of CAR-NK-92 Cells
Challenges and Coping Strategies
Defects in the Transfected Vector
Off-Target Effects
Findings
Conclusions and Perspectives
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