Advancements and challenges in CAR-NK cell therapy for cancer treatment

Zhengshui Xu; Yu Li; Yundong Zhou; Changchun Ye; Junjie Kuang; Chengliang Yin; Danwen Zhao; Hui Guo; Narmatha Chellamani; Manimurugan Shanmuganathan; João Conde; Shiyuan Liu

doi:10.1016/j.tibtech.2025.12.020

Advancements and challenges in CAR-NK cell therapy for cancer treatment

Trends Biotechnol. 2026 Feb 16:S0167-7799(25)00541-4. doi: 10.1016/j.tibtech.2025.12.020. Online ahead of print.

Authors

Zhengshui Xu¹, Yu Li², Yundong Zhou³, Changchun Ye⁴, Junjie Kuang⁵, Chengliang Yin⁶, Danwen Zhao², Hui Guo⁷, Narmatha Chellamani⁸, Manimurugan Shanmuganathan⁹, João Conde¹⁰, Shiyuan Liu¹¹

Affiliations

¹ Department of Thoracic Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, China; Ministry of Education, Key Laboratory of Surgery Critical Care and Life Support (Xi'an Jiaotong University), Xi'an, Shanxi 710061, China.
² Department of Thoracic Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, China.
³ The Second Department of Oncology, Huizhou First Hospital, Huizhou, Guangdong, China.
⁴ Department of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
⁵ Department of Oncology, Liuzhou People's Hospital, Guangxi Medical University, No. 8, Wenchang Road, Chengzhong District, Liuzhou, Guangxi 545006, China.
⁶ Medical Innovation Research Department, Chinese PLA General Hospital, Beijing 100853, China.
⁷ Department of Medical Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, China.
⁸ Faculty of Computers and Information Technology, University of Tabuk, Tabuk, Kingdom of Saudi Arabia.
⁹ Faculty of Computers and Information Technology, University of Tabuk, Tabuk, Kingdom of Saudi Arabia. Electronic address: mmurugan@ut.edu.sa.
¹⁰ Comprehensive Health Research Centre (CHRC), NOVA Medical School, Faculdade de Ciências Médicas, NMS|FCM, Universidade NOVA de Lisboa, Lisboa, Portugal. Electronic address: joao.conde@nms.unl.pt.
¹¹ Department of Thoracic Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, China; Ministry of Education, Key Laboratory of Surgery Critical Care and Life Support (Xi'an Jiaotong University), Xi'an, Shanxi 710061, China. Electronic address: liushiyuan@xjtu.edu.cn.

PMID: 41702798
DOI: 10.1016/j.tibtech.2025.12.020

Abstract

Chimeric antigen receptor natural killer (CAR-NK) cell therapy is an emerging cancer treatment offering advantages over CAR-T therapy, including reduced risks of cytokine release syndrome and graft-versus-host disease. This review highlights how genetic engineering enhances natural killer cells' innate tumor-killing abilities through CAR expression. Preclinical and clinical studies show promising antitumor responses, yet challenges remain, such as ensuring in vivo persistence, overcoming the immunosuppressive tumor microenvironment, and addressing manufacturing hurdles. Strategies such as cytokine support, combination therapies, and novel CAR designs are explored to improve efficacy. Future directions include personalized approaches, novel antigen targets, and artificial intelligence integration. CAR-NK therapy holds strong potential as a safe, scalable, and effective modality in cancer immunotherapy.

Keywords: CAR-NK; CAR-T cell therapy; cancer treatment; cell therapy.

Publication types

Review