Reprogramming natural killer cells for cancer therapy

Kexin Wang; Linqin Wang; Yiyun Wang; Lu Xiao; Jieping Wei; Yongxian Hu; Dongrui Wang; He Huang

doi:10.1016/j.ymthe.2024.01.027

Reprogramming natural killer cells for cancer therapy

Mol Ther. 2024 Jan 24:S1525-0016(24)00027-3. doi: 10.1016/j.ymthe.2024.01.027. Online ahead of print.

Authors

Kexin Wang¹, Linqin Wang¹, Yiyun Wang¹, Lu Xiao², Jieping Wei¹, Yongxian Hu³, Dongrui Wang⁴, He Huang⁵

Affiliations

¹ Bone Marrow Transplantation Center, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China; Liangzhu Laboratory, Hangzhou, Zhejiang Province, China; Institute of Hematology, Zhejiang University, Hangzhou, Zhejiang Province, China; Zhejiang Province Engineering Research Center for Stem Cell and Immunity Therapy, Hangzhou, Zhejiang Province, China.
² Emory University School of Medicine, Atlanta, GA 30322, USA.
³ Bone Marrow Transplantation Center, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China; Liangzhu Laboratory, Hangzhou, Zhejiang Province, China; Institute of Hematology, Zhejiang University, Hangzhou, Zhejiang Province, China; Zhejiang Province Engineering Research Center for Stem Cell and Immunity Therapy, Hangzhou, Zhejiang Province, China. Electronic address: 1313016@zju.edu.cn.
⁴ Bone Marrow Transplantation Center, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China; Liangzhu Laboratory, Hangzhou, Zhejiang Province, China; Institute of Hematology, Zhejiang University, Hangzhou, Zhejiang Province, China; Zhejiang Province Engineering Research Center for Stem Cell and Immunity Therapy, Hangzhou, Zhejiang Province, China. Electronic address: dongrui-wang@zju.edu.cn.
⁵ Bone Marrow Transplantation Center, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China; Liangzhu Laboratory, Hangzhou, Zhejiang Province, China; Institute of Hematology, Zhejiang University, Hangzhou, Zhejiang Province, China; Zhejiang Province Engineering Research Center for Stem Cell and Immunity Therapy, Hangzhou, Zhejiang Province, China. Electronic address: huanghe@zju.edu.cn.

PMID: 38273655
DOI: 10.1016/j.ymthe.2024.01.027

Abstract

The last decade has seen rapid development in the field of cellular immunotherapy, particularly in regard to chimeric antigen receptor (CAR)-modified T cells. However, challenges, such as severe treatment-related toxicities and inconsistent quality of autologous products, have hindered the broader use of CAR-T cell therapy, highlighting the need to explore alternative immune cells for cancer targeting. In this regard, natural killer (NK) cells have been extensively studied in cellular immunotherapy and were found to exert cytotoxic effects without being restricted by human leukocyte antigen and have a lower risk of causing graft-versus-host disease; making them favorable for the development of readily available "off-the-shelf" products. Clinical trials utilizing unedited NK cells or reprogrammed NK cells have shown early signs of their effectiveness against tumors. However, limitations, including limited in vivo persistence and expansion potential, remained. To enhance the antitumor function of NK cells, advanced gene-editing technologies and combination approaches have been explored. In this review, we summarize current clinical trials of antitumor NK cell therapy, provide an overview of innovative strategies for reprogramming NK cells, which include improvements in persistence, cytotoxicity, trafficking and the ability to counteract the immunosuppressive tumor microenvironment, and also discuss some potential combination therapies.

Keywords: CAR; NK cells; cancer; genetic engineering; immunotherapy.

Publication types

Review