The onco-embryonic antigen ROR1 is a target of chimeric antigen T cells for colorectal cancer

Shangsen Meng; Ming Li; Le Qin; Jiang Lv; Di Wu; Diwei Zheng; Heng Jia; Dongmei Chen; Qiting Wu; Youguo Long; Zhaoyang Tang; Yanlai Tang; Lihua Yang; Yao Yao; Xuequn Luo; Peng Li

doi:10.1016/j.intimp.2023.110402

The onco-embryonic antigen ROR1 is a target of chimeric antigen T cells for colorectal cancer

Int Immunopharmacol. 2023 Aug:121:110402. doi: 10.1016/j.intimp.2023.110402. Epub 2023 Jun 8.

Authors

Shangsen Meng¹, Ming Li², Le Qin³, Jiang Lv⁴, Di Wu³, Diwei Zheng³, Heng Jia⁵, Dongmei Chen³, Qiting Wu³, Youguo Long³, Zhaoyang Tang⁶, Yanlai Tang⁷, Lihua Yang⁸, Yao Yao³, Xuequn Luo⁹, Peng Li¹⁰

Affiliations

¹ School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, China; China-New Zealand Joint Laboratory on Biomedicine and Health, State Key Laboratory of Respiratory Disease, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
² China-New Zealand Joint Laboratory on Biomedicine and Health, State Key Laboratory of Respiratory Disease, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China; Department of Health Sciences, Institute of Physical Science and Information Technology, Anhui University, Hefei, China.
³ China-New Zealand Joint Laboratory on Biomedicine and Health, State Key Laboratory of Respiratory Disease, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
⁴ China-New Zealand Joint Laboratory on Biomedicine and Health, State Key Laboratory of Respiratory Disease, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China; Key Laboratory of Biological Targeting Diagnosis, Therapy and Rehabilitation of Guangdong Higher Education Institutes, The Fifth Affiliated Hospital of Guangzhou Medical University, China.
⁵ China-New Zealand Joint Laboratory on Biomedicine and Health, State Key Laboratory of Respiratory Disease, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China; Department of Chemistry and Research Center for Chemical Biology and Omics Analysis, School of Science, Southern University of Science and Technology, Shenzhen 518055, China.
⁶ Guangdong Zhaotai In Vivo Biomedicine Co. Ltd., Guangzhou 510700, China.
⁷ Department of Paediatrics, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510080, China.
⁸ Department of Paediatrics, Zhujiang Hospital, Southern China Medical University, Guangzhou, Guangdong 510280, China.
⁹ Department of Paediatrics, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510080, China. Electronic address: l-xuequn@126.com.
¹⁰ School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, China; China-New Zealand Joint Laboratory on Biomedicine and Health, State Key Laboratory of Respiratory Disease, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China; Key Laboratory of Biological Targeting Diagnosis, Therapy and Rehabilitation of Guangdong Higher Education Institutes, The Fifth Affiliated Hospital of Guangzhou Medical University, China; Department of Surgery of the Faculty of Medicine, The Chinese University of Hong Kong (CUHK), China; Centre for Regenerative Medicine and Health, Hong Kong Institute of Science & Innovation, Chinese Academy of Sciences, Hong Kong SAR, China. Electronic address: li_peng@gibh.ac.cn.

PMID: 37301125
DOI: 10.1016/j.intimp.2023.110402

Abstract

Colorectal cancer is globally ranked second in both incidence and mortality rate. It usually develops during the middle or late stages of diagnosis, and is characterized by easy metastasis, poor prognosis, and a significant decline in postoperative quality of life. ROR1 is an excellent oncoembryonic antigen in numerous immunotherapy treatments for tumors. Additionally, it is overexpressed in colorectal cancer. To fill the void in CRC treatment with ROR1 as a target of CAR-T immunotherapy, we designed and prepared antiROR1-CART. This third-generation CAR-T cell can effectively inhibit the growth of colorectal cancer in vitro and in vivo.

Keywords: CAR-T; CRC; Immunotherapy; ROR1.

MeSH terms

Cell Line, Tumor
Colorectal Neoplasms* / therapy
Humans
Immunotherapy, Adoptive
Quality of Life
Receptor Tyrosine Kinase-like Orphan Receptors / genetics
Receptors, Antigen, T-Cell
T-Lymphocytes*

Substances

Receptors, Antigen, T-Cell
ROR1 protein, human
Receptor Tyrosine Kinase-like Orphan Receptors