Development of TSHR-CAR NK-92 cells for Differentiated Thyroid Cancer

Jiahui Zhou; Chengcheng Zhang; Weibo Mao; Yiling Zhu; Huan Zhao; Ruozhen Han; You Peng; Gang Pan; Yang Fang

doi:10.1016/j.mce.2024.112251

Development of TSHR-CAR NK-92 cells for Differentiated Thyroid Cancer

Mol Cell Endocrinol. 2024 Apr 24:589:112251. doi: 10.1016/j.mce.2024.112251. Online ahead of print.

Authors

Jiahui Zhou¹, Chengcheng Zhang², Weibo Mao³, Yiling Zhu⁴, Huan Zhao⁵, Ruozhen Han⁶, You Peng⁷, Gang Pan⁸, Yang Fang⁹

Affiliations

¹ Department of Pathology, LiShui Central Hospital, The Fifth Hospital Affiliated to Wenzhou Medical University, Zhejiang Province, China. Electronic address: 1007113580@qq.com.
² Core Facilities, Zhejiang University School of Medicine, Zhejiang Province, China. Electronic address: 481955196@qq.com.
³ Department of Pathology, LiShui Central Hospital, The Fifth Hospital Affiliated to Wenzhou Medical University, Zhejiang Province, China. Electronic address: mao5231668@163.com.
⁴ Department of Pathology, LiShui Central Hospital, The Fifth Hospital Affiliated to Wenzhou Medical University, Zhejiang Province, China. Electronic address: 15325179798@189.cn.
⁵ Department of Pathology, LiShui Central Hospital, The Fifth Hospital Affiliated to Wenzhou Medical University, Zhejiang Province, China. Electronic address: 376923236@qq.com.
⁶ Radiotherapy Center, Wenzhou Central Hospital, Zhejiang Province, China. Electronic address: 939355286@qq.com.
⁷ Department of Surgical Oncology, Affiliated Hangzhou First People's Hospital, School of Medicine, Westlake University, Zhejiang Province, China. Electronic address: doctor3663@163.com.
⁸ Department of Surgical Oncology, Affiliated Hangzhou First People's Hospital, School of Medicine, Westlake University, Zhejiang Province, China. Electronic address: xjxsh@163.com.
⁹ Department of Surgical Oncology, Affiliated Hangzhou First People's Hospital, School of Medicine, Westlake University, Zhejiang Province, China. Electronic address: bravefang@163.com.

PMID: 38670219
DOI: 10.1016/j.mce.2024.112251

Abstract

Differentiated thyroid cancer (DTC) is the predominant type of thyroid cancer, with some patients experiencing relapse, distant metastases, or refractoriness, revealing limited treatment options. Chimeric antigen receptor (CAR)-modified Natural Killer (NK) cells are revolutionary therapeutic agents effective against various resistant cancers. Thyroid-stimulating hormone receptor (TSHR) expression in DTC provides a unique tumor-specific target for CAR therapy. Here, we developed an innovative strategy for treating DTC using modified NK-92 cells armed with a TSHR-targeted CAR. The modified cells showed enhanced cytotoxicity against TSHR-positive DTC cell lines and exhibited elevated degranulation and cytokine release. After undergoing irradiation, the cells effectively halted their proliferative capacity while maintaining potent targeted killing ability. Transfer of these irradiation-treated cells into NSG mice with DTC tumors resulted in profound tumor suppression. NK-92 cells modified with TSHR-CAR offer a promising, off-the-shelf option for advancing DTC immunotherapy.

Keywords: Differentiated thyroid cancer; NK cell; TSHR-CAR; Tumor treatment.