CAR-T cells targeting CD38 and LMP1 exhibit robust antitumour activity against NK/T cell lymphoma

Hongwen Li; Wenting Song; Jiazhuo Wu; Zhuangzhuang Shi; Yuyang Gao; Jiwei Li; Lijuan Han; Jianxiang Zhang; Zhaoming Li; Yong Li; Mingzhi Zhang

doi:10.1186/s12916-023-03040-0

CAR-T cells targeting CD38 and LMP1 exhibit robust antitumour activity against NK/T cell lymphoma

BMC Med. 2023 Aug 30;21(1):330. doi: 10.1186/s12916-023-03040-0.

Authors

Hongwen Li^#^{1

2}, Wenting Song^#^{1

2

3}, Jiazhuo Wu^{1

2

3}, Zhuangzhuang Shi^{1

2

3}, Yuyang Gao^{1

2

3}, Jiwei Li^{1

2}, Lijuan Han¹, Jianxiang Zhang¹, Zhaoming Li^{1

2}, Yong Li⁴, Mingzhi Zhang^{5

6}

Affiliations

¹ Department of Oncology, Jianshendong Rd., The First Affiliated Hospital of Zhengzhou University, No. 1, Zhengzhou, 450052, Henan Province, China.
² State Key Laboratory of Esophageal Cancer Prevention and Treatment and Henan Key Laboratory for Esophageal Cancer Research, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
³ Academy of Medical Sciences of Zhengzhou University, Zhengzhou, Henan, China.
⁴ Department of Medicine, Baylor College of Medicine, Houston, TX, USA.
⁵ Department of Oncology, Jianshendong Rd., The First Affiliated Hospital of Zhengzhou University, No. 1, Zhengzhou, 450052, Henan Province, China. mingzhi_zhang1@163.com.
⁶ State Key Laboratory of Esophageal Cancer Prevention and Treatment and Henan Key Laboratory for Esophageal Cancer Research, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China. mingzhi_zhang1@163.com.

^# Contributed equally.

Abstract

Background: Natural killer/T cell lymphoma (NKTCL) is an aggressive lymphoma with a poor prognosis. Chimeric antigen receptor-transduced T (CAR-T) cell therapy has become a promising immunotherapeutic strategy against haematologic malignancies.

Methods: In this study, four CAR-T cell lines (CD38-CAR, LMP1-CAR, CD38-LMP1 tandem CAR 1 and CD38-LMP1 tandem CAR 2) were generated. The effect of CAR-T cells against NKTCL cells was evaluated both in vitro and in vivo. Expression of T cell activation markers and cytokines produced by CAR-T cells were detected by flow cytometry.

Results: The four CAR-T cell lines could effectively eliminate malignant NKTCL cells. They could be activated and produce inflammatory cytokines in a target-dependent manner. In vivo tests showed that the CAR-T cells exhibited significant antitumour effects in a xenotransplanted NKTCL mouse model.

Conclusions: In summary, four CAR-T cell lines exhibited significant cytotoxicity against NKTCL cells both in vitro and in vivo. These results indicated the effective therapeutic promise of CD38 and LMP1 CAR-T cells in NKTCL.

Keywords: CAR-T; CD38; Immunotherapy; LMP1; NKTCL; Tandem.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cytokines
Disease Models, Animal
Lymphoma, T-Cell*
Mice
Receptors, Chimeric Antigen* / genetics
T-Lymphocytes

Substances

Receptors, Chimeric Antigen
Cytokines