Targeting CD276 by CAR-T cells induces regression of esophagus squamous cell carcinoma in xenograft mouse models

Yujing Xuan; Yuqiao Sheng; Daiqun Zhang; Kai Zhang; Zhen Zhang; Yu Ping; Shumin Wang; Xiaojuan Shi; Jingyao Lian; Kangdong Liu; Yi Zhang; Feng Li

Translational Oncology (Aug 2021)

Targeting CD276 by CAR-T cells induces regression of esophagus squamous cell carcinoma in xenograft mouse models

Yujing Xuan,
Yuqiao Sheng,
Daiqun Zhang,
Kai Zhang,
Zhen Zhang,
Yu Ping,
Shumin Wang,
Xiaojuan Shi,
Jingyao Lian,
Kangdong Liu,
Yi Zhang,
Feng Li

Affiliations

Yujing Xuan: Biotherapy Center, Cancer Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China; Henan Key Laboratory for Tumor Immunology and Biotherapy, Zhengzhou, Henan, China; State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou, Henan, China
Yuqiao Sheng: Medical Research Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
Daiqun Zhang: Biotherapy Center, Cancer Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China; Henan Key Laboratory for Tumor Immunology and Biotherapy, Zhengzhou, Henan, China; State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou, Henan, China
Kai Zhang: Biotherapy Center, Cancer Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China; Henan Key Laboratory for Tumor Immunology and Biotherapy, Zhengzhou, Henan, China; State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou, Henan, China
Zhen Zhang: Biotherapy Center, Cancer Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China; Henan Key Laboratory for Tumor Immunology and Biotherapy, Zhengzhou, Henan, China; State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou, Henan, China
Yu Ping: Biotherapy Center, Cancer Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China; Henan Key Laboratory for Tumor Immunology and Biotherapy, Zhengzhou, Henan, China; State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou, Henan, China
Shumin Wang: Biotherapy Center, Cancer Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China; Henan Key Laboratory for Tumor Immunology and Biotherapy, Zhengzhou, Henan, China; State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou, Henan, China
Xiaojuan Shi: Biotherapy Center, Cancer Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China; Henan Key Laboratory for Tumor Immunology and Biotherapy, Zhengzhou, Henan, China; State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou, Henan, China
Jingyao Lian: Biotherapy Center, Cancer Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China; Henan Key Laboratory for Tumor Immunology and Biotherapy, Zhengzhou, Henan, China; State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou, Henan, China
Kangdong Liu: Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, China; State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou, Henan, China; China-US Hormel (Henan) Cancer Institute, Zhengzhou, Henan, China; Corresponding author at: Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, 100 Science Avenue, Zhengzhou, Henan 450052, China.
Yi Zhang: Biotherapy Center, Cancer Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China; Henan Key Laboratory for Tumor Immunology and Biotherapy, Zhengzhou, Henan, China; School of Life Sciences, Zhengzhou University, Zhengzhou, Henan, China; State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou, Henan, China; Corresponding authors at: Biotherapy Center, the First Affiliated Hospital of Zhengzhou University, 1 Jianshe East Road, Zhengzhou, Henan 450052, China.
Feng Li: Biotherapy Center, Cancer Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China; Henan Key Laboratory for Tumor Immunology and Biotherapy, Zhengzhou, Henan, China; State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou, Henan, China; Corresponding authors at: Biotherapy Center, the First Affiliated Hospital of Zhengzhou University, 1 Jianshe East Road, Zhengzhou, Henan 450052, China.

Journal volume & issue: Vol. 14, no. 8
p. 101138

Abstract

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Esophageal cancer, including esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC), has a poor prognosis and limited therapeutic options. Chimeric antigen receptor (CAR)-T cells represent a potential ESCC treatment. In this study, we examined CD276 expression in healthy and esophageal tumor tissues and explored the tumoricidal potential of CD276-targeting CAR-T cells in ESCC. CD276 was strongly and homogenously expressed in ESCC and EAC tumor lesions but mildly in healthy tissues, representing a good target for CAR-T cell therapy. We generated CD276-directed CAR-T cells with a humanized antigen-recognizing domain and CD28 or 4–1BB co-stimulation. CD276-specific CAR-T cells efficiently killed ESCC tumor cells in an antigen-dependent manner both in vitro and in vivo. In patient-derived xenograft models, CAR-T cells induced tumor regression and extended mouse survival. In addition, CAR-T cells generated from patient T cells demonstrated potent cytotoxicity against autologous tumor cells. Our study indicates that CD276 is an attractive target for ESCC therapy, and CD276-targeting CAR-T cells are worth testing in ESCC clinical trials.

Published in Translational Oncology

ISSN: 1944-7124 (Print); 1936-5233 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: https://www.journals.elsevier.com/translational-oncology/

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